Tumor Type-Dependent Function of the Par3 Polarity Protein in Skin Tumorigenesis

Cologne Cluster of Excellence in Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, 50931 Cologne, Germany.
Cancer cell (Impact Factor: 23.89). 09/2012; 22(3):389-403. DOI: 10.1016/j.ccr.2012.08.004
Source: PubMed

ABSTRACT Cell polarization is crucial during development and tissue homeostasis and is regulated by conserved proteins of the Scribble, Crumbs, and Par complexes. In mouse skin tumorigenesis, Par3 deficiency results in reduced papilloma formation and growth. Par3 mediates its tumor-promoting activity through regulation of growth and survival, since Par3 deletion increases apoptosis and reduces growth in vivo and in vitro. In contrast, Par3-deficient mice are predisposed to formation of keratoacanthomas, cutaneous tumors thought to originate from different cellular origin and frequently observed in humans. Par3 expression is reduced in both mouse and human keratoacanthomas, indicating tumor-suppressive properties of Par3. Our results identify a dual function of Par3 in skin cancer, with both pro-oncogenic and tumor-suppressive activity depending on the tumor type.

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    • "It is also believed that PAR proteins may be involved in multiple aspects of oncogenesis because a relationship exists between polarity dysfunction and cancer progression [14] [15] [16]. Defective or overexpressed PAR-3 proteins have been described in other cancers related to tumor development or metastases formation, including breast cancer [17] [18], hepatocellular carcinoma [19], or skin tumors [20]. In ccRCC, along with lower survival rates, we recently showed that the migration of tumor cells might be promoted by the overexpression of PAR-3 and that the cytoskeleton organization was significantly altered [13]. "
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