Cell polarity and the pathogenesis of skin cancer

How epithelia coordinate cell and tissue structure with growth and metabolic activity to control morphogenesis, homeostasis and regeneration of tissues is a fundamental question in biology. Altered regulation of epithelial cell/tissue architecture disturbs tissue homeostasis and regeneration and promotes cancer initiation, progression and metastasis in addition to a range of inflammatory diseases. The Niessen laboratory asks how molecular regulation of cell shape controls the formation and maintenance of epithelial tissues. More specifically, we addresses how cadherin mediated cell-cell adhesion and aPKC-controlled polarity signaling integrate with metabolic insulin/IGF-1 signaling in the skin epidermis to control stem cell renewal, differentiation, tissue integrity, growth and inflammation in the skin. We also address how altered DNA damage pathways and external insults, such as UV radiation, interfere with these pathways to drive altered regeneration and/or skin cancer.