During tumor progression the well-ordered architecture of the mammary gland becomes disrupted as hyperproliferative cells accumulate in the luminal space of ducts and lobules. Over time the neoplastic cells can invade into the stroma where they can access the vasculature system and disseminate to distant sites throughout the body. Although the induction of invasive growth is a key step in the metastatic cascade, how breast cancer cells become invasive remains poorly understood. Using an organotypic culture system and animal models we propose to determine (1) how cell motility is regulated by intracellular signaling pathways during collective invasion;(2) how mammary fibroblasts induce collective invasion and (3) how subpopulations of neoplastic cells trigger collective invasion. Deciphering the requirements for breast cancer invasion could identify targets for therapeutic intervention in both the tumor and the microenvironment.
Distant metastases are responsible for nearly all breast cancer patient deaths. A critical step leading to the development of metastases is the invasion of tumor cells into connective tissue. We will investigate how tumor cells become invasive with the goals of more accurately identifying which patients are at risk of developing metastases and identifying targets of therapeutic intervention.
|Maine, Erin A; Westcott, Jill M; Prechtl, Amanda M et al. (2016) The cancer-testis antigens SPANX-A/C/D and CTAG2 promote breast cancer invasion. Oncotarget 7:14708-26|
|Dang, Tuyen T; Westcott, Jill M; Maine, Erin A et al. (2016) Î”Np63Î± induces the expression of FAT2 and Slug to promote tumor invasion. Oncotarget 7:28592-611|
|Dang, Tuyen T; Esparza, Matthew A; Maine, Erin A et al. (2015) Î”Np63Î± Promotes Breast Cancer Cell Motility through the Selective Activation of Components of the Epithelial-to-Mesenchymal Transition Program. Cancer Res 75:3925-35|
|Westcott, Jill M; Prechtl, Amanda M; Maine, Erin A et al. (2015) An epigenetically distinct breast cancer cell subpopulation promotes collective invasion. J Clin Invest 125:1927-43|
|Dbouk, Hashem A; Weil, Lauren M; Perera, G K Sachith et al. (2014) Actions of the protein kinase WNK1 on endothelial cells are differentially mediated by its substrate kinases OSR1 and SPAK. Proc Natl Acad Sci U S A 111:15999-6004|
|Dang, Tuyen T; Prechtl, Amanda M; Pearson, Gray W (2011) Breast cancer subtype-specific interactions with the microenvironment dictate mechanisms of invasion. Cancer Res 71:6857-66|