Cadherin control of invasive growth in morphogenes.. (CCinG)
Cadherin control of invasive growth in morphogenesis and cancer
Start date: Jan 1, 2013,
End date: Dec 31, 2014
Cadherin-based cell-cell junctions regulate tissue architecture by coordinating multicellular growth and polarity. In addition to the ubiquitously expressed and widely studied E-cadherin, epithelia express other, more tissue-specific classical cadherins, often particularly during developmental epithelial rearrangements. These additional cadherins recently also have been implicated in tumor progression, but their expression and function is poorly understood.I recently demonstrated that different classical cadherin subtypes have distinct roles in branching morphogenesis. I hypothesize that cell-cell junction control in invasive growth of developmental branching morphogenesis is recapitulated in collective cancer invasion, where tumor cells invade as strands that maintain cadherin-based cell-cell contacts. The aim is therefore to determine how stage-dependent regulation of distinct cadherins control these processes, using the following objectives:1. To test that co-expression of E-cadherin and other cadherins control cell migration and rearrangement of the extracellular matrix and, thus, invasive physiological growth.2. To define the role of co-expressed cadherins in collective invasive growth and resistance in cancer.To demonstrate how cadherins accessory to E-cadherin control physiological collective invasion and growth, and how this is recapitulated in an aberrant fashion during invasive growth of epithelial cancers, I will contrast models for branching morphogenesis of kidney and mammary epithelium to neoplastic invasion of kidney and breast cancer cells.
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