Deciphering the principles of skin cancer
The Iden lab investigates functions of mammalian polarity proteins in skin homeostasis, stress responses, and cancer. We study how deregulated polarity signaling impacts on cyto-architecture, survival and cell death using genetically modified mice in developmental and disease models as well as advanced in vitro systems. Our aim is to better understand how cell polarity signaling contributes to fundamental tissue functions and to age-associated pathologies to reveal novel directions for targeted therapies. Melanoma represents a fatal skin cancer with increasing incidence in the Western world and frequent metastasis. A serious problem in controlling melanoma is the marked ability of melanoma cells to reversibly switch between states of high or low differentiation and motility, thereby quickly adapting to environmental changes and evading immune surveillance. Thus, identifying strategies to restrict phenotypic switching is crucial to develop melanoma therapies with long-term success. Conserved polarity proteins couple cell shape to control of growth, migration and differentiation. We previously uncovered important roles of the Par3 polarity complex in skin homeostasis and different epithelial cancers, in line with frequent dysregulation in human cancer. Our recent work revealed novel extrinsic functions of epidermal polarity proteins in suppressing melanoma through regulation of keratinocyte-melanocyte interactions. We now aim at deciphering the in vivo relevance of polarity signaling in melanoma progression, and exploring how polarity proteins contribute to clinical resistance mechanisms.