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Arthur Mercurio, PhD

Mechanisms that underlie the genesis of invasive carcinoma and the progression to metastatic disease are the major interests of the Mercurio laboratory, with a specific focus on breast and colon carcinoma. Given that all carcinomas arise from epithelia, our approach is rooted in the cell biology of mammary gland and colonic epithelia and it emphasizes understanding those changes in epithelial organization and function that contribute to invasive carcinoma

A major area of emphasis in the Mercurio laboratory is to understand the signaling pathways associated with integrin engagement and modulation of extracellular matrix-dependent signals contributing to tumor cell survival and tumor cell invasiveness. This process, generally defined as epithelial-mesenchymal transition is thought to play a critical role in the process of tumor cell dissemination to distant organs, i.e. metastasis

Current Research Projects in the Mercurio Laboratory

National Institutes of Health-National Cancer Institute

  • R01CA107548: Epithelial Mesenchymal Transition and Invasive Carcinoma

    Epithelial-Mesenchymal Transition: The epithelial to mesenchymal transition (EMT) is a useful paradigm for studying the genesis of invasive carcinoma because it reflects events that occur at the invasive front of carcinomas and that persist in aggressive tumors. The defining event for EMT is disruption of E-cadherin-mediated cell-cell adhesion, which results in loss of epithelial morphology and acquisition of a motile, mesenchymal phenotype. The EMT process that occurs in carcinomas, however, also involves aspects of epithelial de-differentiation and the neo-expression of proteins associated with epithelial development. We are using in vitro models of the EMT as a foundation for elucidating mechanisms involved in the migration and survival of aggressive carcinomas and for the identification of potential therapeutic targets. The data obtained from these models are substantiated with studies on human tumor specimens and mouse models of colon cancer.

  • R01CA080789: Integrin Function and Signaling in Carcinoma Progression

    The Integrin 6 4 and Invasive Carcinoma: 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 pivotal role in functions associated with carcinoma progression, including migration, invasion and survival. What has emerged from these studies is the premise that 6 4 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 the contribution of 6 4 to progression using mouse models and they are elucidating the signaling mechanisms by which 6 4 exerts its influence on cell functions linked to progression.

  •  R01CA089209: Mechanisms of Breast Carcinoma Survival

    VEGF Signaling and Invasive Carcinoma: One important consequence of the EMT is that it facilitates the ability of carcinoma cells to survive in the absence of cell-cell contact and in the presence of stress imposed by the tumor microenvironment (e.g., hypoxia). One mechanism for such survival that we have established is the elaboration of autocrine signaling loops as a consequence of EMT. Specifically, we have shown that the expression of both VEGF and specific VEGF receptors (Neuropilin and Flt-1) is induced during the EMT and that a VEGF autocrine loop involving these receptors is essential for the survival of many carcinoma cells. In this direction, we are pursuing the signaling mechanisms by which Neuropilin and Flt-1 promote the survival of invasive carcinoma cells.

  • BLTR0706837: Glyolysis, IRS-2 and Metastatic Breast Cancer

    We propose to obtain definitive evidence to link IRS-2 to glycolysis in breast tumor cells using both a mouse model and cells isolated from huma breast tumors. We also propose to explain how IRS-2 controls glycolysis. The information obtained should be of immediate use to facilitate the development of targeted drugs that block both glycolysis and IRS-2 in breast cancer.