117 Determinants of epithelial morphogenic change during oncogenic transformation

Aged, healthy skin contains cells with cancer-associated mutations yet remains aphenotypic, suggesting flexible management of oncogenic stress during homeostasis. Our lab found β-catenin expression in follicular epidermis induced aberrant growths that regressed. Although a hallmark epithelial derived tumors is loss homeostatic tissue organization, the not only resisted malignant transformation, but also returned to equilibrium. However, molecular and cell state determinants morphogenic change cancer initiation due remain unclear. As such, we sought track function mutant by directly visualizing its localization cortex as junctional component nucleus Wnt effector. This required longitudinally resolving mosaic tagged live animals. Thus, established system inducibly expressed GFP β-cateninΔ90 adult murine skin, imaging over time two-photon microscopy. expected, from interfollicular invaginated into dermal collagen before becoming eliminated. intensity stem nuclei positively correlated growth formation, linking this change. recent studies show differentiated mediate epidermal disruption, investigated whether differentiating cells, roughly 40 percent all could provoke similar phenotype. These failed yield even 30 days post-induction, context mutation determines architectural outcome. Mutant had little no nuclear β-catenin. Attempting rescue phenotype, knocked down E-cadherin, reasoning cell-cell adhesion promotes tumor development decreasing cortical sink would increase Curiously, though levels rose, formed. Collectively, these findings indicate coordination between identity are necessary disruption