Project Details
Projekt
Role of Integrin-linked kinase in skin homeostasis and carcinogenesis
Applicant
Professorin Dr. Sara A. Wickström, Ph.D.
Subject Area
Dermatology
Term
from 2014 to 2018
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 262258314
Epidermal (skin) tumors are the most common type of cancer in Europe. The epidermis is exposed to a wide range of environmental insults, including ultraviolet irradiation and chemical carcinogens. As a result, epidermal keratinocytes have a high risk of acquiring an oncogenic mutation. However, relatively few skin cancers develop because most cells that acquire mutations are either lost through the normal process of terminal differentiation or activation of a permanent state of cell cycle arrest termed senescence. Therefore, the analysis of factors that can co-operate with oncogenes is critical for understanding the mechanisms of cancer progression. We have previously analyzed mice lacking Integrin-linked kinase (ILK), a central effector of beta1 integrin adhesion receptor, in their skin. These mice display a profound defect in the balance between proliferation and terminal differentiation in the epidermis. Therefore it is clear that ILK regulates epidermal homeostasis and the proliferation-differentiation switch of the epidermal keratinocytes, but the molecular mechanisms of this regulation are still unclear. The aim of this project is to understand how the central adhesion signaling adaptor Integrin-linked kinase (ILK) regulates SC homeostasis in the skin, in particular through its effect on the matrix remodeling. We further aim to uncover how impairments in SC homeostasis and cell fate decisions contribute to skin carcinogenesis. The long-term goal of these studies is to precisely understand how cell-matrix interactions, through their ability to regulate growth factor bioavailability and activation, regulate cancer initiation and progression in humans.
DFG Programme
Research Grants
