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Role of the Par3 complex in skin carcinogenesis

Coworkers: Annika Graband, Soriba Letzian, Michael Saynisch

Non-melanoma skin cancer is among the most common cancers worldwide with a still increasing incidence due to longer life expectancy and rising sun exposure. Interestingly, the tumor environment plays a decisive role in skin cancer progression. Alterations in polarity and architecture of tumor cells are hallmarks of cancers and have been implicated in cancer growth, invasion and metastasis. The mechanisms that determine how the tumor cyto-architecture and its surroundings communicate to either promote or inhibit cancer are largely unknown. Previously we have identified a crucial role for the polarity protein Par3 in the regulation of epidermal differentiation and survival (see Ali et al., JID 2016; Mescher & Iden, 2015). Most importantly, epidermal inactivation of Par3 inhibits papilloma formation but promotes keratoacanthoma formation (see Iden et al., Cancer Cell 2012). These tumors are thought to arise from different cell populations, indicating a context-dependent role for Par3 in different skin tumors. We currently assess the underlying mechanisms by which alterations in the Par3 complex control tumor initiation and progression, and address how these alterations in tumor cell architecture affect the communication with the microenvironment to either drive or inhibit tumorigenesis.