Project Details
Projekt
Molecular and genetic interaction of the polarity proteins Par3 and aPKC in skin carcinogenesis
Subject Area
Dermatology
Cell Biology
Cell Biology
Term
from 2014 to 2018
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 252588851
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 proteins aPKCl and Par3, which can form a complex, in the regulation of epidermal stem cell maintenance, keratinocyte differentiation and survival as well as skin inflammation. Most importantly, epidermal inactivation of Par3 inhibits papilloma formation but promotes keratoacanthoma formation. These tumors are thought to arise from different cell populations, indicating a context-dependent role for Par3 in different skin tumors. In the present proposal we will ask whether aPKCl and Par3 have overlapping or different roles in skin tumor promotion and suppression by combining our expertise and different mouse models generated in our laboratories. We will address the underlying mechanisms by which alterations in Par3 and aPKCl 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.
DFG Programme
Research Grants
