The other face of MUC1 protein in cancer progression – the role of MUC1-C subunit
Journal Title: Advances in Hygiene and Experimental Medicine - Year 2019, Vol 73, Issue
Abstract
MUC1 is high-molecular-weight glycoprotein which is widely expressed on epithelial cell layers of various organs and is aberrantly overexpressed in most human carcinomas such as breast, ovarian or colon cancer. MUC1 contains three domains: short cytoplasmic and transmembrane domains, and a long extracellular domain. The protein is translated as a single polypeptide that undergoes auto-cleavage into two subunits: MUC1-N and MUC1-C, that form a stable noncovalent complex at the cell membrane. In normal epithelial cells, MUC1 expression is restricted to the apical side of the cells. During cancer transformation there is a loss of cell polarity and MUC1-C is found over the entire cell surface while MUC1-N is shed from the surface of carcinoma cells. As the result of depolarization, MUC1-C interacts with receptor tyrosine kinases (RTKs), such as EGFR and activates intracellular pathways which are important for cancer progression. Overexpression of MUC1 is also associated with the accumulation of MUC1-C in the cytoplasm and targeting of this subunit to the nucleus or mitochondria. Nuclear localization of MUC1-C is associated with activation of gene families involved in oncogenesis or cancer metabolism. Other results have shown that MUC1-C localizes to the mitochondrial outer membrane, where it blocks stress induced apoptosis. Recent studies have been directed at the MUC1-C subunit which reminds to be attractive target for the development of anti-cancer agents. In this review, the role of MUC1-C in cancer progression is discussed.<br/><br/>
Authors and Affiliations
Alicja M. Kmiecik, Piotr Dzięgiel, Maciej Ugorski
Keywords
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- EP ID EP432509
- DOI 10.5604/01.3001.0012.8399
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