Objetivo
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.
Ámbito científico
Convocatoria de propuestas
FP7-PEOPLE-2011-IIF
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Régimen de financiación
MC-IIF - International Incoming Fellowships (IIF)Coordinador
6525 XZ Nijmegen
Países Bajos