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

• Published in: Cancer cell Vol. 22; no. 3; pp. 389 - 403
• Main Authors: Iden, Sandra, van Riel, Wilhelmina E., Schäfer, Ronny, Song, Ji-Ying, Hirose, Tomonori, Ohno, Shigeo, Collard, John G.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 11.09.2012
• Subjects: Animals; Cell Adhesion Molecules - deficiency; Cell Adhesion Molecules - genetics; Cell Adhesion Molecules - metabolism; Cell Polarity; Cell Proliferation; Cell Transformation, Neoplastic; Cells, Cultured; Keratinocytes - metabolism; Keratoacanthoma - genetics; Keratoacanthoma - metabolism; Keratoacanthoma - pathology; Mice; Mice, Transgenic; Protein Kinase C - metabolism; Skin - metabolism; Skin Neoplasms - genetics; Skin Neoplasms - metabolism; Skin Neoplasms - pathology
• ISSN: 1535-6108; 1878-3686
• DOI: 10.1016/j.ccr.2012.08.004

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. [Display omitted] ► Par3 deletion reduces Ras-driven papilloma formation and growth ► Loss of Par3 mislocalizes aPKC and Ras, reduces growth, and increases apoptosis ► Par3 deletion predisposes mice to keratoacanthomas also found in humans ► Dependent on the tumor type, Par3 can either promote or suppress skin tumorigenesis