Project Details
Projekt
The role of XIAP and XIAP-antagonization through mitochondria in melanoma metastasis
Subject Area
Dermatology
Cell Biology
Cell Biology
Term
from 2014 to 2018
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 265862083
Malignant melanomas are the most aggressive skin tumors. Depending on the vertical tumor depth melanomas metastasize early to distant tissues. Metastasis is a highly regulated evolutionary process, culminating in the prevalence of rare tumor cells that acquire the capacity to migrate and resist to hostile microenvironments. According to the widely held model of metastasis, rare subpopulations of cells within the primary tumor acquire advantageous genetic alterations over time, which enable these cells to metastasize and to form new solid tumors at distant sites. Recently we demonstrated a direct association of the X-linked inhibitor of apoptosis protein (XIAP) expression with melanoma progression. The elevated XIAP expression however did not correlate with patient outcome upon chemotherapy suggesting that XIAP in metastatic melanoma may interfere with cellular regulatory circuits other than cell death. Indeed recent data suggested that XIAP modulates cellular motility by directing cytoskeleton reorganization. The overall goal of this project is to understand the pathophysiological role of XIAP in melanoma metastasis and to unravel the molecular mechanisms underlying XIAP accumulation in metastatic melanoma. We will specifically address following questins: 1) What is the pathophysiological role of XIAP in melanoma metastasis? 2) Does XIAP/SMAC crosstalk impact on cell motility and migration of metastatic melanoma? and 3) How and why does XIAP accumulate in metastatic melanoma? This project will physiologically examine the role of XIAP and mitochondria during melanoma metastasis and their targeting as a therapeutic modality in metastatic melanoma.
DFG Programme
Research Grants
