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    Arthur M Mercurio PhD

    TitleChair and Professor
    InstitutionUniversity of Massachusetts Medical School
    DepartmentCancer Biology
    AddressUniversity of Massachusetts Medical School
    364 Plantation Street, LRB
    Worcester MA 01605
    Phone508-856-8676
      Other Positions
      InstitutionUMMS - Graduate School of Biomedical Sciences
      DepartmentCancer Biology

      InstitutionUMMS - Graduate School of Biomedical Sciences
      DepartmentImmunology and Virology

      InstitutionUMMS - Graduate School of Biomedical Sciences
      DepartmentInterdisciplinary Graduate Program

      InstitutionUMMS - Graduate School of Biomedical Sciences
      DepartmentMD/PhD Program

      InstitutionUMMS - Graduate School of Biomedical Sciences
      DepartmentTranslational Science

      InstitutionUMMS - Programs, Centers and Institutes
      DepartmentBioinformatics and Integrative Biology

        Overview 
        Narrative

        ACADEMIC BACKGROUND

        Arthur Mercurio received his B.S. in Biochemistry from Rutgers University in 1975 and a Ph.D. in Cell Biology from Columbia University in 1981. He was a Postdoctoral Fellow in the Center for Cancer Research at M.I.T. from 1981-1985. In 1986, he joined the faculty at Harvard Medical School and the Beth Israel Deaconess Medical Center. He was the Director of the Division of Cancer Biology and Angiogenesis at BIDMC until 2005 when he became Vice Chairman of the Department of Cancer Biology at the University of Massachusetts Medical School and Interim Chair in 2010. Dr. Mercurio is a recipient of the American Cancer Society Junior Faculty and Faculty Research Awards, and he was an Honorary Professor at the University of Copenhagen.

        TRANSLATIONAL CANCER CELL BIOLOGY

        We are interested in the initiation and progression of epithelial-derived tumors (carcinomas), especially aggressive, poorly differentiated tumors. Our research projects emphasize molecular cell biology but they derive from the analysis and clinical behavior of carcinomas. Our goal is to identify mechanisms that account for the loss of differentiation and the highly aggressive behavior of these tumors, and to exploit these mechanisms to improve prognosis and therapy. Ongoing projects in the lab include studies on:

        Regulation and Function of Integrins

        The lab has a long-standing interest in the a6 integrins (a6ß1 and a6ß4). These integrins have pivotal roles in the biology of carcinomas as demonstrated by our work and that of others. The a6ß1 integrin (CD49f) is an established marker for many populations of tumor stem/initiating cells including those present in breast and prostate carcinomas and it is essential for the function of these cells. Current studies on a6ß1 involve its regulation by Neuropilin-2 and VEGF signaling (see below) and elucidating the mechanism by which it contributes to the function of tumor stem/initiating cells. We are continuing our studies on the integrin a6ß4 (referred to as ‘ß4 integrin’) in this context. The primary function of this integrin, which is expressed on the basal surface of most epithelia, is to anchor the epithelium to laminins in the basement membrane and maintain epithelial integrity. Our lab pioneered studies that established that this integrin also plays a significant role in functions associated with carcinoma progression, including migration, invasion and survival, and that it is often expressed in poorly differentiated carcinomas. What has emerged from these studies is the premise that the ß4 integrin plays a dominant role in progression through its ability to influence other receptors and key signaling pathways. Given these findings and their implications, current projects are assessing mechanisms that regulate ß4 integrin gene expression in human cancers, the role of specific microRNAs in regulating ß4 integrin function and signaling and the contribution of ß4 integrin to epithelial biology and carcinoma progression using mouse models of specific carcinomas.

        VEGF Function and Signaling in Carcinoma Cells

        This project is based on the hypothesis that VEGF receptors expressed on carcinoma cells mediate VEGF signaling and that VEGF signaling in epithelial cells contributes to tumor initiation. This hypothesis challenges the notion that the function of VEGF in cancer is limited to angiogenesis and that therapeutic approaches based on the inhibition of VEGF and its receptors target only angiogenesis. We are most interested in a specific class of VEGF receptors termed the neuropilins (NRPs). NRP1 and NRP2 were identified initially as neuronal receptors for semaphorins, but they also function as VEGF receptors on tumor cells. We are particularly interested in NRP2 because our recent findings indicate that its contribution to breast tumorigenesis is significant. NRP2 expression correlates with progression and poor outcome in women with breast cancer, and its expression is associated with aggressive, triple-negative breast cancers. Moreover, our data indicate that NRP2 expression is induced by oncogenic stimuli that promote mammary tumor formation and they suggest that it has a causal role in tumorigenesis. We also discovered that NRP2 is highly enriched in tumor-initiating cells isolated from triple-negative tumors and that it can regulate the function of the a6ß1 integrin (CD49f), a marker of tumor-initiating cells. An important implication of our findings is that NRP2 is a prime target for therapeutic intervention, a highly feasible possibility because function-blocking antibodies are available for clinical trials. This issue is timely because the FDA has recommended discontinuing the use of Avastin (bevacizumab) for treating breast cancer because it has not been shown to be effective. Bevacizumab, however, does not inhibit the VEGF/NRP2 interaction, strengthening the rationale for targeting NRP2 directly. Based on existing data, we postulate that VEGF/NRP2 signaling cooperates with oncogenic stimuli to drive the formation of breast cancers by promoting the functions of tumor-initiating cells, especially the function and signaling properties of the a6ß1 integrin.

        We are also pursuing the contribution of VEGF/NRP2 to prostate cancer. This project is based on our novel findings that PTEN deletion induces JNK/Jun-dependent NRP2 expression, NRP2 contributes to the growth of PTEN-null prostate carcinoma cells in soft agar and as xenografts, and NRP2 expression correlates with Gleason grade. The role of VEGF/NRP2 signaling in prostate tumorigenesis can be explained by our exciting discovery that NRP2 facilitates the expression of Bmi-1, a transcriptional repressor that has a critical role in the function of prostate stem and tumor initiating cells. We have also shown that NRP2 suppresses the IGF-1 receptor (IGF-1R) by a mechanism that involves transcriptional repression by Bmi-1 and, as a consequence, confers resistance to IGF-1R therapy of prostate carcinoma. In fact, we have found that NRP2 expressing prostate tumors are resistant to IGF-1R therapy. This hypothesis is significant because several IGF-1R inhibitors are in clinical trials but the mechanisms to account for patient response to these inhibitors are largely unknown. Given that clinical trials of the VEGF Ab bevacizumab have been disappointing, we are targeting NRP2 directly on tumor cells in combination with IGF-1R inhibition as a novel and a potentially potent approach for treating prostate carcinoma.


        Regulation of Epithelial Fate and Carcinoma Differentiation by Estrogen Receptors
        We are interested in the hypothesis that ligand-dependent activation of estrogen receptors (either ERa or ß) sustains epithelial differentiation and that loss of this activation in carcinomas contributes to a more de-differentiated, aggressive phenotype. This hypothesis is supported by the observation that ERa-negative breast carcinomas are typically less differentiated and more aggressive than ERa-positive tumors. Also, the loss of ERß in high-grade prostate carcinomas is also linked to de-differentiation and highly invasive behavior. We reported that a key function of ERß and its specific ligand 5a-androstane-3ß,17ß-diol (3ß-adiol) is to maintain an epithelial phenotype and repress mesenchymal characteristics in prostate carcinoma. The mechanism involves ERß-mediated destabilization of HIF-1a and transcriptional repression of HIF-1 target genes including VEGF-A. This mechanism is extremely important and relevant because we demonstrated that high Gleason grade tumors exhibit significantly elevated expression of HIF-1a but clinically relevant hypoxia is not seen in localized primary prostate cancer including high-grade tumors. These observations indicate that loss of ERß in prostate cancer mimics hypoxia by stabilizing HIF-1a. The mechanism by which ERß destabilizes HIF-1a is under investigation and we hypothesize that this mechanism is critical for maintaining an epithelial state and preventing a mesenchymal transition. The loss of ERß that characterizes high-grade, aggressive prostate cancer results in increased VEGF expression in tumor cells and consequent autocrine VEGF/NRP2 signaling as described above.


        RNA Binding Proteins in Aggressive Carcinomas
        This project is based on the finding that the expression of IGFII mRNA-binding protein 3 (IMP3) is associated with highly aggressive cancers, including triple-negative breast carcinomas. We are pursuing the hypothesis that IMP3 has an essential role in maintaining a de-differentiated state characteristic of high-grade tumors and that it functions in this capacity by interacting with and facilitating the expression of specific mRNAs whose proteins products promote epithelial de-differentiation.



        Rotation Projects

        Rotation Projects

        Rotation projects are designed to expose students to the molecular cell biology of solid tumors and to provide them with an appreciation for translational cancer research. Specific rotation projects, which are focused on the major themes of the lab, include:

        Function and Regulation of Integrins (Cell Adhesion Receptors) in Cancer

        • Epigenetic mechanisms that regulate integrin gene expression in human cancers
        • Regulation of integrin expression and function during the EMT
        • Role of specfic microRNAs (miRs) in regulating integrin function and signaling
        • Contribution of integrins to carcinoma progression using mouse models of breast carcinoma

        Vascular Endothelial Growth Factor (VEGF) Signaling, EMT and Carcinoma Progression

        • Function and expression of VEGF receptors in carcinoma cells
        • Regulation of VEGF transcription in response to EMT stimuli
        • Role of miRs in regulating VEGF receptors and signaling
        • Contribution of VEGF signaling to the behavior of aggressive, de-differentiated carcinomas

        Nuclear Hormone Receptors and EMT

        • Role of estrogen receptors in regulating the EMT
        • Regulation of VEGF transcription by estrogen receptors


        Bibliographic 
        selected publications
        List All   |   Timeline
        1. Goel HL, Gritsko T, Pursell B, Chang C, Shultz LD, Greiner DL, Norum JH, Toftgard R, Shaw LM, Mercurio AM. Regulated Splicing of the a6 Integrin Cytoplasmic Domain Determines the Fate of Breast Cancer Stem Cells. Cell Rep. 2014 May 8; 7(3):747-61.
          View in: PubMed
        2. Gao Y, Yang M, Jiang Z, Woda BA, Mercurio AM, Qin J, Huang X, Zhang F. IMP3 expression is associated with poor outcome and epigenetic deregulation in intrahepatic cholangiocarcinoma. Hum Pathol. 2014 Jun; 45(6):1184-91.
          View in: PubMed
        3. Goel HL, Mercurio AM. VEGF targets the tumour cell. Nat Rev Cancer. 2013 Nov 22; 13(12):871-82.
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        4. Chang C, Yang X, Pursell B, Mercurio AM. Id2 complexes with the SNAG domain of Snai1 inhibiting Snai1-mediated repression of integrin ß4. Mol Cell Biol. 2013 Oct; 33(19):3795-804.
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        5. Samanta S, Pursell B, Mercurio AM. IMP3 protein promotes chemoresistance in breast cancer cells by regulating breast cancer resistance protein (ABCG2) expression. J Biol Chem. 2013 May 3; 288(18):12569-73.
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        6. Mak P, Chang C, Pursell B, Mercurio AM. Estrogen receptor ß sustains epithelial differentiation by regulating prolyl hydroxylase 2 transcription. Proc Natl Acad Sci U S A. 2013 Mar 19; 110(12):4708-13.
          View in: PubMed
        7. Goel HL, Pursell B, Chang C, Shaw LM, Mao J, Simin K, Kumar P, Vander Kooi CW, Shultz LD, Greiner DL, Norum JH, Toftgard R, Kuperwasser C, Mercurio AM. GLI1 regulates a novel neuropilin-2/a6ß1 integrin based autocrine pathway that contributes to breast cancer initiation. EMBO Mol Med. 2013 Apr; 5(4):488-508.
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        8. Goel HL, Mercurio AM. Enhancing integrin function by VEGF/neuropilin signaling: implications for tumor biology. Cell Adh Migr. 2012 Nov-Dec; 6(6):554-60.
          View in: PubMed
        9. Goel HL, Chang C, Pursell B, Leav I, Lyle S, Xi HS, Hsieh CC, Adisetiyo H, Roy-Burman P, Coleman IM, Nelson PS, Vessella RL, Davis RJ, Plymate SR, Mercurio AM. VEGF/neuropilin-2 regulation of Bmi-1 and consequent repression of IGF-IR define a novel mechanism of aggressive prostate cancer. Cancer Discov. 2012 Oct; 2(10):906-21.
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        10. Gerson KD, Maddula VS, Seligmann BE, Shearstone JR, Khan A, Mercurio AM. Effects of ß4 integrin expression on microRNA patterns in breast cancer. Biol Open. 2012 Jul 15; 1(7):658-66.
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        11. Jiao B, Ma H, Shokhirev MN, Drung A, Yang Q, Shin J, Lu S, Byron M, Kalantry S, Mercurio AM, Lawrence JB, Hoffmann A, Bach I. Paternal RLIM/Rnf12 is a survival factor for milk-producing alveolar cells. Cell. 2012 Apr 27; 149(3):630-41.
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        12. Gerson KD, Shearstone JR, Maddula VS, Seligmann BE, Mercurio AM. Integrin ß4 regulates SPARC protein to promote invasion. J Biol Chem. 2012 Mar 23; 287(13):9835-44.
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        13. Samanta S, Sharma VM, Khan A, Mercurio AM. Regulation of IMP3 by EGFR signaling and repression by ERß: implications for triple-negative breast cancer. Oncogene. 2012 Nov 1; 31(44):4689-97.
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        14. Goel HL, Pursell B, Standley C, Fogarty K, Mercurio AM. Neuropilin-2 regulates a6ß1 integrin in the formation of focal adhesions and signaling. J Cell Sci. 2012 Jan 15; 125(Pt 2):497-506.
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        15. Cellurale C, Girnius N, Jiang F, Cavanagh-Kyros J, Lu S, Garlick DS, Mercurio AM, Davis RJ. Role of JNK in mammary gland development and breast cancer. Cancer Res. 2012 Jan 15; 72(2):472-81.
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        16. Lu D, Yang X, Jiang NY, Woda BA, Liu Q, Dresser K, Mercurio AM, Rock KL, Jiang Z. IMP3, a new biomarker to predict progression of cervical intraepithelial neoplasia into invasive cancer. Am J Surg Pathol. 2011 Nov; 35(11):1638-45.
          View in: PubMed
        17. Fröhlich C, Nehammer C, Albrechtsen R, Kronqvist P, Kveiborg M, Sehara-Fujisawa A, Mercurio AM, Wewer UM. ADAM12 produced by tumor cells rather than stromal cells accelerates breast tumor progression. Mol Cancer Res. 2011 Nov; 9(11):1449-61.
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        18. Goel HL, Bae D, Pursell B, Gouvin LM, Lu S, Mercurio AM. Neuropilin-2 promotes branching morphogenesis in the mouse mammary gland. Development. 2011 Jul; 138(14):2969-76.
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        19. Moriarty CH, Pursell B, Mercurio AM. miR-10b targets Tiam1: implications for Rac activation and carcinoma migration. J Biol Chem. 2010 Jul 2; 285(27):20541-6.
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        20. Mak P, Leav I, Pursell B, Bae D, Yang X, Taglienti CA, Gouvin LM, Sharma VM, Mercurio AM. ERbeta impedes prostate cancer EMT by destabilizing HIF-1alpha and inhibiting VEGF-mediated snail nuclear localization: implications for Gleason grading. Cancer Cell. 2010 Apr 13; 17(4):319-32.
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        21. Ghosh R, Lipson KL, Sargent KE, Mercurio AM, Hunt JS, Ron D, Urano F. Transcriptional regulation of VEGF-A by the unfolded protein response pathway. PLoS One. 2010; 5(3):e9575.
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        22. Mehrotra S, Languino LR, Raskett CM, Mercurio AM, Dohi T, Altieri DC. IAP regulation of metastasis. Cancer Cell. 2010 Jan 19; 17(1):53-64.
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        23. Yang X, Pursell B, Lu S, Chang TK, Mercurio AM. Regulation of beta 4-integrin expression by epigenetic modifications in the mammary gland and during the epithelial-to-mesenchymal transition. J Cell Sci. 2009 Jul 15; 122(Pt 14):2473-80.
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        24. Pankratz SL, Tan EY, Fine Y, Mercurio AM, Shaw LM. Insulin receptor substrate-2 regulates aerobic glycolysis in mouse mammary tumor cells via glucose transporter 1. J Biol Chem. 2009 Jan 23; 284(4):2031-7.
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        25. Bae D, Lu S, Taglienti CA, Mercurio AM. Metabolic stress induces the lysosomal degradation of neuropilin-1 but not neuropilin-2. J Biol Chem. 2008 Oct 17; 283(42):28074-80.
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        26. Lu S, Simin K, Khan A, Mercurio AM. Analysis of integrin beta4 expression in human breast cancer: association with basal-like tumors and prognostic significance. Clin Cancer Res. 2008 Feb 15; 14(4):1050-8.
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        27. Merdek KD, Yang X, Taglienti CA, Shaw LM, Mercurio AM. Intrinsic signaling functions of the beta4 integrin intracellular domain. J Biol Chem. 2007 Oct 12; 282(41):30322-30.
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        28. Folgiero V, Bachelder RE, Bon G, Sacchi A, Falcioni R, Mercurio AM. The alpha6beta4 integrin can regulate ErbB-3 expression: implications for alpha6beta4 signaling and function. Cancer Res. 2007 Feb 15; 67(4):1645-52.
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        29. Bates RC, Pursell BM, Mercurio AM. Epithelial-mesenchymal transition and colorectal cancer: gaining insights into tumor progression using LIM 1863 cells. Cells Tissues Organs. 2007; 185(1-3):29-39.
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        30. Yoon SO, Shin S, Mercurio AM. Ras stimulation of E2F activity and a consequent E2F regulation of integrin alpha6beta4 promote the invasion of breast carcinoma cells. Cancer Res. 2006 Jun 15; 66(12):6288-95.
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        31. Bellovin DI, Simpson KJ, Danilov T, Maynard E, Rimm DL, Oettgen P, Mercurio AM. Reciprocal regulation of RhoA and RhoC characterizes the EMT and identifies RhoC as a prognostic marker of colon carcinoma. Oncogene. 2006 Nov 2; 25(52):6959-67.
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        32. Bellovin DI, Bates RC, Muzikansky A, Rimm DL, Mercurio AM. Altered localization of p120 catenin during epithelial to mesenchymal transition of colon carcinoma is prognostic for aggressive disease. Cancer Res. 2005 Dec 1; 65(23):10938-45.
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        33. Lipscomb EA, Simpson KJ, Lyle SR, Ring JE, Dugan AS, Mercurio AM. The alpha6beta4 integrin maintains the survival of human breast carcinoma cells in vivo. Cancer Res. 2005 Dec 1; 65(23):10970-6.
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        34. Mercurio AM, Lipscomb EA, Bachelder RE. Non-angiogenic functions of VEGF in breast cancer. J Mammary Gland Biol Neoplasia. 2005 Oct; 10(4):283-90.
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        35. Lipscomb EA, Mercurio AM. Mobilization and activation of a signaling competent alpha6beta4integrin underlies its contribution to carcinoma progression. Cancer Metastasis Rev. 2005 Sep; 24(3):413-23.
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        36. Kveiborg M, Fröhlich C, Albrechtsen R, Tischler V, Dietrich N, Holck P, Kronqvist P, Rank F, Mercurio AM, Wewer UM. A role for ADAM12 in breast tumor progression and stromal cell apoptosis. Cancer Res. 2005 Jun 1; 65(11):4754-61.
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        37. Bates RC, Mercurio AM. The epithelial-mesenchymal transition (EMT) and colorectal cancer progression. Cancer Biol Ther. 2005 Apr; 4(4):365-70.
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        38. Yoon SO, Shin S, Mercurio AM. Hypoxia stimulates carcinoma invasion by stabilizing microtubules and promoting the Rab11 trafficking of the alpha6beta4 integrin. Cancer Res. 2005 Apr 1; 65(7):2761-9.
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        39. Govindarajan B, Shah A, Cohen C, Arnold RS, Schechner J, Chung J, Mercurio AM, Alani R, Ryu B, Fan CY, Cuezva JM, Martinez M, Arbiser JL. Malignant transformation of human cells by constitutive expression of platelet-derived growth factor-BB. J Biol Chem. 2005 Apr 8; 280(14):13936-43.
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        40. Bates RC, Bellovin DI, Brown C, Maynard E, Wu B, Kawakatsu H, Sheppard D, Oettgen P, Mercurio AM. Transcriptional activation of integrin beta6 during the epithelial-mesenchymal transition defines a novel prognostic indicator of aggressive colon carcinoma. J Clin Invest. 2005 Feb; 115(2):339-47.
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        41. Bachelder RE, Yoon SO, Franci C, de Herreros AG, Mercurio AM. Glycogen synthase kinase-3 is an endogenous inhibitor of Snail transcription: implications for the epithelial-mesenchymal transition. J Cell Biol. 2005 Jan 3; 168(1):29-33.
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        42. Simpson KJ, Dugan AS, Mercurio AM. Functional analysis of the contribution of RhoA and RhoC GTPases to invasive breast carcinoma. Cancer Res. 2004 Dec 1; 64(23):8694-701.
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        43. Bates RC, DeLeo MJ, Mercurio AM. The epithelial-mesenchymal transition of colon carcinoma involves expression of IL-8 and CXCR-1-mediated chemotaxis. Exp Cell Res. 2004 Oct 1; 299(2):315-24.
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        44. Chung J, Yoon S, Datta K, Bachelder RE, Mercurio AM. Hypoxia-induced vascular endothelial growth factor transcription and protection from apoptosis are dependent on alpha6beta1 integrin in breast carcinoma cells. Cancer Res. 2004 Jul 15; 64(14):4711-6.
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        45. Chung J, Yoon SO, Lipscomb EA, Mercurio AM. The Met receptor and alpha 6 beta 4 integrin can function independently to promote carcinoma invasion. J Biol Chem. 2004 Jul 30; 279(31):32287-93.
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        46. Rabinovitz I, Tsomo L, Mercurio AM. Protein kinase C-alpha phosphorylation of specific serines in the connecting segment of the beta 4 integrin regulates the dynamics of type II hemidesmosomes. Mol Cell Biol. 2004 May; 24(10):4351-60.
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        47. Chung J, Mercurio AM. Contributions of the alpha6 integrins to breast carcinoma survival and progression. Mol Cells. 2004 Apr 30; 17(2):203-9.
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        48. Mercurio AM, Bachelder RE, Bates RC, Chung J. Autocrine signaling in carcinoma: VEGF and the alpha6beta4 integrin. Semin Cancer Biol. 2004 Apr; 14(2):115-22.
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        49. DeClerck YA, Mercurio AM, Stack MS, Chapman HA, Zutter MM, Muschel RJ, Raz A, Matrisian LM, Sloane BF, Noel A, Hendrix MJ, Coussens L, Padarathsingh M. Proteases, extracellular matrix, and cancer: a workshop of the path B study section. Am J Pathol. 2004 Apr; 164(4):1131-9.
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        50. Bates RC, Goldsmith JD, Bachelder RE, Brown C, Shibuya M, Oettgen P, Mercurio AM. Flt-1-dependent survival characterizes the epithelial-mesenchymal transition of colonic organoids. Curr Biol. 2003 Sep 30; 13(19):1721-7.
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        51. Bachelder RE, Lipscomb EA, Lin X, Wendt MA, Chadborn NH, Eickholt BJ, Mercurio AM. Competing autocrine pathways involving alternative neuropilin-1 ligands regulate chemotaxis of carcinoma cells. Cancer Res. 2003 Sep 1; 63(17):5230-3.
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        52. Kawaguchi N, Sundberg C, Kveiborg M, Moghadaszadeh B, Asmar M, Dietrich N, Thodeti CK, Nielsen FC, Möller P, Mercurio AM, Albrechtsen R, Wewer UM. ADAM12 induces actin cytoskeleton and extracellular matrix reorganization during early adipocyte differentiation by regulating beta1 integrin function. J Cell Sci. 2003 Oct 1; 116(Pt 19):3893-904.
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        53. Mercurio AM. Invasive skin carcinoma--Ras and alpha6beta4 integrin lead the way. Cancer Cell. 2003 Mar; 3(3):201-2.
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        54. Bates RC, Mercurio AM. Tumor necrosis factor-alpha stimulates the epithelial-to-mesenchymal transition of human colonic organoids. Mol Biol Cell. 2003 May; 14(5):1790-800.
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        55. Lipscomb EA, Dugan AS, Rabinovitz I, Mercurio AM. Use of RNA interference to inhibit integrin (alpha6beta4)-mediated invasion and migration of breast carcinoma cells. Clin Exp Metastasis. 2003; 20(6):569-76.
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        56. Thodeti CK, Albrechtsen R, Grauslund M, Asmar M, Larsson C, Takada Y, Mercurio AM, Couchman JR, Wewer UM. ADAM12/syndecan-4 signaling promotes beta 1 integrin-dependent cell spreading through protein kinase Calpha and RhoA. J Biol Chem. 2003 Mar 14; 278(11):9576-84.
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        57. Bachelder RE, Wendt MA, Mercurio AM. Vascular endothelial growth factor promotes breast carcinoma invasion in an autocrine manner by regulating the chemokine receptor CXCR4. Cancer Res. 2002 Dec 15; 62(24):7203-6.
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        58. Chung J, Bachelder RE, Lipscomb EA, Shaw LM, Mercurio AM. Integrin (alpha 6 beta 4) regulation of eIF-4E activity and VEGF translation: a survival mechanism for carcinoma cells. J Cell Biol. 2002 Jul 8; 158(1):165-74.
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        59. Morena A, Riccioni S, Marchetti A, Polcini AT, Mercurio AM, Blandino G, Sacchi A, Falcioni R. Expression of the beta 4 integrin subunit induces monocytic differentiation of 32D/v-Abl cells. Blood. 2002 Jul 1; 100(1):96-106.
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        60. Mercurio AM. Lessons from the alpha2 integrin knockout mouse. Am J Pathol. 2002 Jul; 161(1):3-6.
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        61. Rabinovitz I, Gipson IK, Mercurio AM. Traction forces mediated by alpha6beta4 integrin: implications for basement membrane organization and tumor invasion. Mol Biol Cell. 2001 Dec; 12(12):4030-43.
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        62. O'Connor KL, Mercurio AM. Protein kinase A regulates Rac and is required for the growth factor-stimulated migration of carcinoma cells. J Biol Chem. 2001 Dec 21; 276(51):47895-900.
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        63. Mercurio AM, Rabinovitz I, Shaw LM. The alpha 6 beta 4 integrin and epithelial cell migration. Curr Opin Cell Biol. 2001 Oct; 13(5):541-5.
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        64. Bachelder RE, Crago A, Chung J, Wendt MA, Shaw LM, Robinson G, Mercurio AM. Vascular endothelial growth factor is an autocrine survival factor for neuropilin-expressing breast carcinoma cells. Cancer Res. 2001 Aug 1; 61(15):5736-40.
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        65. Tani TT, Mercurio AM. PDZ interaction sites in integrin alpha subunits. T14853, TIP/GIPC binds to a type I recognition sequence in alpha 6A/alpha 5 and a novel sequence in alpha 6B. J Biol Chem. 2001 Sep 28; 276(39):36535-42.
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        66. Bachelder RE, Wendt MA, Fujita N, Tsuruo T, Mercurio AM. The cleavage of Akt/protein kinase B by death receptor signaling is an important event in detachment-induced apoptosis. J Biol Chem. 2001 Sep 14; 276(37):34702-7.
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        67. Mercurio AM, Bachelder RE, Chung J, O'Connor KL, Rabinovitz I, Shaw LM, Tani T. Integrin laminin receptors and breast carcinoma progression. J Mammary Gland Biol Neoplasia. 2001 Jul; 6(3):299-309.
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        68. Mercurio AM, Rabinovitz I. Towards a mechanistic understanding of tumor invasion--lessons from the alpha6beta 4 integrin. Semin Cancer Biol. 2001 Apr; 11(2):129-41.
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        69. Mercurio AM, Bachelder RE, Rabinovitz I, O'Connor KL, Tani T, Shaw LM. The metastatic odyssey: the integrin connection. Surg Oncol Clin N Am. 2001 Apr; 10(2):313-28, viii-ix.
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        70. Gambaletta D, Marchetti A, Benedetti L, Mercurio AM, Sacchi A, Falcioni R. Cooperative signaling between alpha(6)beta(4) integrin and ErbB-2 receptor is required to promote phosphatidylinositol 3-kinase-dependent invasion. J Biol Chem. 2000 Apr 7; 275(14):10604-10.
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        71. Lotz MM, Rabinovitz I, Mercurio AM. Intestinal restitution: progression of actin cytoskeleton rearrangements and integrin function in a model of epithelial wound healing. Am J Pathol. 2000 Mar; 156(3):985-96.
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        72. O'Connor KL, Nguyen BK, Mercurio AM. RhoA function in lamellae formation and migration is regulated by the alpha6beta4 integrin and cAMP metabolism. J Cell Biol. 2000 Jan 24; 148(2):253-8.
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        73. Bachelder RE, Ribick MJ, Marchetti A, Falcioni R, Soddu S, Davis KR, Mercurio AM. p53 inhibits alpha 6 beta 4 integrin survival signaling by promoting the caspase 3-dependent cleavage of AKT/PKB. J Cell Biol. 1999 Nov 29; 147(5):1063-72.
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        74. Rabinovitz I, Toker A, Mercurio AM. Protein kinase C-dependent mobilization of the alpha6beta4 integrin from hemidesmosomes and its association with actin-rich cell protrusions drive the chemotactic migration of carcinoma cells. J Cell Biol. 1999 Sep 6; 146(5):1147-60.
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        75. Bachelder RE, Marchetti A, Falcioni R, Soddu S, Mercurio AM. Activation of p53 function in carcinoma cells by the alpha6beta4 integrin. J Biol Chem. 1999 Jul 16; 274(29):20733-7.
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        76. Chen MS, Almeida EA, Huovila AP, Takahashi Y, Shaw LM, Mercurio AM, White JM. Evidence that distinct states of the integrin alpha6beta1 interact with laminin and an ADAM. J Cell Biol. 1999 Feb 8; 144(3):549-61.
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        77. O'Connor KL, Shaw LM, Mercurio AM. Release of cAMP gating by the alpha6beta4 integrin stimulates lamellae formation and the chemotactic migration of invasive carcinoma cells. J Cell Biol. 1998 Dec 14; 143(6):1749-60.
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        78. Homan SM, Mercurio AM, LaFlamme SE. Endothelial cells assemble two distinct alpha6beta4-containing vimentin-associated structures: roles for ligand binding and the beta4 cytoplasmic tail. J Cell Sci. 1998 Sep; 111 ( Pt 18):2717-28.
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        79. Carloni V, Romanelli RG, Mercurio AM, Pinzani M, Laffi G, Cotrozzi G, Gentilini P. Knockout of alpha6 beta1-integrin expression reverses the transformed phenotype of hepatocarcinoma cells. Gastroenterology. 1998 Aug; 115(2):433-42.
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        80. Wei J, Shaw LM, Mercurio AM. Regulation of mitogen-activated protein kinase activation by the cytoplasmic domain of the alpha6 integrin subunit. J Biol Chem. 1998 Mar 6; 273(10):5903-7.
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        81. Rabinovitz I, Mercurio AM. The integrin alpha6beta4 functions in carcinoma cell migration on laminin-1 by mediating the formation and stabilization of actin-containing motility structures. J Cell Biol. 1997 Dec 29; 139(7):1873-84.
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        82. Shaw LM, Rabinovitz I, Wang HH, Toker A, Mercurio AM. Activation of phosphoinositide 3-OH kinase by the alpha6beta4 integrin promotes carcinoma invasion. Cell. 1997 Dec 26; 91(7):949-60.
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        83. Wewer UM, Shaw LM, Albrechtsen R, Mercurio AM. The integrin alpha 6 beta 1 promotes the survival of metastatic human breast carcinoma cells in mice. Am J Pathol. 1997 Nov; 151(5):1191-8.
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        84. Wei J, Shaw LM, Mercurio AM. Integrin signaling in leukocytes: lessons from the alpha6beta1 integrin. J Leukoc Biol. 1997 Apr; 61(4):397-407.
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        85. Lise M, Loda M, Fiorentino M, Mercurio AM, Summerhayes IC, Lavin PT, Jessup JM. Association between sucrase-isomaltase and p53 expression in colorectal cancer. Ann Surg Oncol. 1997 Mar; 4(2):176-83.
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        86. Lotz MM, Nusrat A, Madara JL, Ezzell R, Wewer UM, Mercurio AM. Intestinal epithelial restitution. Involvement of specific laminin isoforms and integrin laminin receptors in wound closure of a transformed model epithelium. Am J Pathol. 1997 Feb; 150(2):747-60.
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        87. Chao C, Lotz MM, Clarke AC, Mercurio AM. A function for the integrin alpha6beta4 in the invasive properties of colorectal carcinoma cells. Cancer Res. 1996 Oct 15; 56(20):4811-9.
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        88. Shaw LM, Chao C, Wewer UM, Mercurio AM. Function of the integrin alpha 6 beta 1 in metastatic breast carcinoma cells assessed by expression of a dominant-negative receptor. Cancer Res. 1996 Mar 1; 56(5):959-63.
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        89. Rabinovitz I, Mercurio AM. The integrin alpha 6 beta 4 and the biology of carcinoma. Biochem Cell Biol. 1996; 74(6):811-21.
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        90. Jessup JM, Lavin PT, Andrews CW, Loda M, Mercurio A, Minsky BD, Mies C, Cukor B, Bleday R, Steele G. Sucrase-isomaltase is an independent prognostic marker for colorectal carcinoma. Dis Colon Rectum. 1995 Dec; 38(12):1257-64.
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        91. Mercurio AM. Laminin receptors: achieving specificity through cooperation. Trends Cell Biol. 1995 Nov; 5(11):419-23.
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        92. Shaw LM, Turner CE, Mercurio AM. The alpha 6A beta 1 and alpha 6B beta 1 integrin variants signal differences in the tyrosine phosphorylation of paxillin and other proteins. J Biol Chem. 1995 Oct 6; 270(40):23648-52.
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        93. Clarke AS, Lotz MM, Chao C, Mercurio AM. Activation of the p21 pathway of growth arrest and apoptosis by the beta 4 integrin cytoplasmic domain. J Biol Chem. 1995 Sep 29; 270(39):22673-6.
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        94. Breen E, Steele G, Mercurio AM. Role of the E-cadherin/alpha-catenin complex in modulating cell-cell and cell-matrix adhesive properties of invasive colon carcinoma cells. Ann Surg Oncol. 1995 Sep; 2(5):378-85.
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        95. Almeida EA, Huovila AP, Sutherland AE, Stephens LE, Calarco PG, Shaw LM, Mercurio AM, Sonnenberg A, Primakoff P, Myles DG, White JM. Mouse egg integrin alpha 6 beta 1 functions as a sperm receptor. Cell. 1995 Jun 30; 81(7):1095-104.
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        96. Byers SW, Sommers CL, Hoxter B, Mercurio AM, Tozeren A. Role of E-cadherin in the response of tumor cell aggregates to lymphatic, venous and arterial flow: measurement of cell-cell adhesion strength. J Cell Sci. 1995 May; 108 ( Pt 5):2053-64.
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        97. Tözeren A, Kleinman HK, Grant DS, Morales D, Mercurio AM, Byers SW. E-selectin-mediated dynamic interactions of breast- and colon-cancer cells with endothelial-cell monolayers. Int J Cancer. 1995 Jan 27; 60(3):426-31.
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        98. Shaw LM, Mercurio AM. Regulation of alpha 6 beta 1 integrin-mediated migration in macrophages. Agents Actions Suppl. 1995; 47:101-6.
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        99. Tözeren A, Kleinman HK, Wu S, Mercurio AM, Byers SW. Integrin alpha 6 beta 4 mediates dynamic interactions with laminin. J Cell Sci. 1994 Nov; 107 ( Pt 11):3153-63.
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        100. Shaw LM, Mercurio AM. Regulation of cellular interactions with laminin by integrin cytoplasmic domains: the A and B structural variants of the alpha 6 beta 1 integrin differentially modulate the adhesive strength, morphology, and migration of macrophages. Mol Biol Cell. 1994 Jun; 5(6):679-90.
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        101. Clarke AS, Lotz MM, Mercurio AM. A novel structural variant of the human beta 4 integrin cDNA. Cell Adhes Commun. 1994 Apr; 2(1):1-6.
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        102. Rossen K, Dahlstrøm KK, Mercurio AM, Wewer UM. Expression of the alpha 6 beta 4 integrin by squamous cell carcinomas and basal cell carcinomas: possible relation to invasive potential? Acta Derm Venereol. 1994 Mar; 74(2):101-5.
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        103. Breen E, Clarke A, Steele G, Mercurio AM. Poorly differentiated colon carcinoma cell lines deficient in alpha-catenin expression express high levels of surface E-cadherin but lack Ca(2+)-dependent cell-cell adhesion. Cell Adhes Commun. 1993 Dec; 1(3):239-50.
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        104. Shaw LM, Mercurio AM. Regulation of alpha 6 beta 1 integrin laminin receptor function by the cytoplasmic domain of the alpha 6 subunit. J Cell Biol. 1993 Nov; 123(4):1017-25.
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        105. Shaw LM, Lotz MM, Mercurio AM. Inside-out integrin signaling in macrophages. Analysis of the role of the alpha 6A beta 1 and alpha 6B beta 1 integrin variants in laminin adhesion by cDNA expression in an alpha 6 integrin-deficient macrophage cell line. J Biol Chem. 1993 May 25; 268(15):11401-8.
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        106. Lotz MM, Andrews CW, Korzelius CA, Lee EC, Steele GD, Clarke A, Mercurio AM. Decreased expression of Mac-2 (carbohydrate binding protein 35) and loss of its nuclear localization are associated with the neoplastic progression of colon carcinoma. Proc Natl Acad Sci U S A. 1993 Apr 15; 90(8):3466-70.
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        107. Messier JM, Shaw LM, Chafel M, Matsudaira P, Mercurio AM. Fimbrin localized to an insoluble cytoskeletal fraction is constitutively phosphorylated on its headpiece domain in adherent macrophages. Cell Motil Cytoskeleton. 1993; 25(3):223-33.
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        108. Andrews CW, O'Hara CJ, Goldman H, Mercurio AM, Silverman ML, Steele GD. Sucrase-isomaltase expression in chronic ulcerative colitis and dysplasia. Hum Pathol. 1992 Jul; 23(7):774-9.
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        109. Lee EC, Lotz MM, Steele GD, Mercurio AM. The integrin alpha 6 beta 4 is a laminin receptor. J Cell Biol. 1992 May; 117(3):671-8.
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        110. Lee EC, Woo HJ, Korzelius CA, Steele GD, Mercurio AM. Carbohydrate-binding protein 35 is the major cell-surface laminin-binding protein in colon carcinoma. Arch Surg. 1991 Dec; 126(12):1498-502.
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        111. Woo HJ, Lotz MM, Jung JU, Mercurio AM. Carbohydrate-binding protein 35 (Mac-2), a laminin-binding lectin, forms functional dimers using cysteine 186. J Biol Chem. 1991 Oct 5; 266(28):18419-22.
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        112. Mercurio AM, Shaw LM. Laminin binding proteins. Bioessays. 1991 Sep; 13(9):469-73.
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        113. Wiltz O, O'Hara CJ, Steele GD, Mercurio AM. Expression of enzymatically active sucrase-isomaltase is a ubiquitous property of colon adenocarcinomas. Gastroenterology. 1991 May; 100(5 Pt 1):1266-78.
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        114. Wewer UM, Mercurio AM, Chung SY, Albrechtsen R. Deoxyribonucleic-binding homeobox proteins are augmented in human cancer. Lab Invest. 1990 Oct; 63(4):447-54.
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        115. Mercurio AM. Laminin: multiple forms, multiple receptors. Curr Opin Cell Biol. 1990 Oct; 2(5):845-9.
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        116. Wiltz O, O'Hara CJ, Steele GD, Mercurio AM. Sucrase-isomaltase: a marker associated with the progression of adenomatous polyps to adenocarcinomas. Surgery. 1990 Aug; 108(2):269-75; discussion 275-6.
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        117. Shaw LM, Messier JM, Mercurio AM. The activation dependent adhesion of macrophages to laminin involves cytoskeletal anchoring and phosphorylation of the alpha 6 beta 1 integrin. J Cell Biol. 1990 Jun; 110(6):2167-74.
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        118. Woo HJ, Shaw LM, Messier JM, Mercurio AM. The major non-integrin laminin binding protein of macrophages is identical to carbohydrate binding protein 35 (Mac-2). J Biol Chem. 1990 May 5; 265(13):7097-9.
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        119. Lotz MM, Korzelius CA, Mercurio AM. Human colon carcinoma cells use multiple receptors to adhere to laminin: involvement of alpha 6 beta 4 and alpha 2 beta 1 integrins. Cell Regul. 1990 Feb; 1(3):249-57.
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        120. Daneker GW, Piazza AJ, Steele GD, Mercurio AM. Interactions of human colorectal carcinoma cells with basement membranes. Analysis and correlation with differentiation. Arch Surg. 1989 Feb; 124(2):183-7.
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        121. Daneker GW, Piazza AJ, Steele GD, Mercurio AM. Relationship between extracellular matrix interactions and degree of differentiation in human colon carcinoma cell lines. Cancer Res. 1989 Feb 1; 49(3):681-6.
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        122. Shaw LM, Mercurio AM. Interferon gamma and lipopolysaccharide promote macrophage adherence to basement membrane glycoproteins. J Exp Med. 1989 Jan 1; 169(1):303-8.
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        123. Mercurio AM, Shaw LM. Macrophage interactions with laminin: PMA selectively induces the adherence and spreading of mouse macrophages on a laminin substratum. J Cell Biol. 1988 Nov; 107(5):1873-80.
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        124. Daneker GW, Mercurio AM, Guerra L, Wolf B, Salem RR, Bagli DJ, Steele GD. Laminin expression in colorectal carcinomas varying in degree of differentiation. Arch Surg. 1987 Dec; 122(12):1470-4.
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        125. Sheares BT, Mercurio AM. Modulation of two distinct galactosyltransferase activities in populations of mouse peritoneal macrophages. J Immunol. 1987 Dec 1; 139(11):3748-52.
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        126. Mercurio AM. Disruption of oligosaccharide processing in murine tumor cells inhibits their susceptibility to lysis by activated mouse macrophages. Proc Natl Acad Sci U S A. 1986 Apr; 83(8):2609-13.
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        127. Mercurio AM, Robbins PW. Activation of mouse peritoneal macrophages alters the structure and surface expression of protein-bound lactosaminoglycans. J Immunol. 1985 Aug; 135(2):1305-12.
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        128. Mercurio AM, Schwarting GA, Robbins PW. Glycolipids of the mouse peritoneal macrophage. Alterations in amount and surface exposure of specific glycolipid species occur in response to inflammation and tumoricidal activation. J Exp Med. 1984 Oct 1; 160(4):1114-25.
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        129. Mercurio AM, Holtzman E. Smooth endoplasmic reticulum and other agranular reticulum in frog retinal photoreceptors. J Neurocytol. 1982 Apr; 11(2):263-93.
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        130. Mercurio AM, Holtzman E. Ultrastructural localization of glycerolipid synthesis in rod cells of the isolated frog retina. J Neurocytol. 1982 Apr; 11(2):295-322.
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        131. Holtzman E, Mercurio AM. Membrane circulation in neurons and photoreceptors: some unresolved issues. Int Rev Cytol. 1980; 67:1-67.
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        132. Holtzman E, Gronowicz G, Mercurio A. Notes on the heterogeneity, circulation, and modification of membranes, with emphasis on secretory cells, photoreceptors, and the toad bladder. Biomembranes. 1979; 10:77-139.
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