title: Tumor type-dependent function of the par3 polarity protein in skin tumorigenesis.
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.
authors.affiliation: Division of Cell Biology I, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands. sandra.iden@uk-koeln.de
authors.forename: Sandra
authors.initials: S
authors.lastname: Iden
authors.forename: Wilhelmina E
authors.initials: WE
authors.lastname: van Riel
authors.forename: Ronny
authors.initials: R
authors.lastname: Schäfer
authors.forename: Ji-Ying
authors.initials: JY
authors.lastname: Song
authors.forename: Tomonori
authors.initials: T
authors.lastname: Hirose
authors.forename: Shigeo
authors.initials: S
authors.lastname: Ohno
authors.forename: John G
authors.initials: JG
authors.lastname: Collard
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D015815:Cell Adhesion Molecules / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins; D016764:Cell Polarity; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D015603:Keratinocytes / Q000378:metabolism; D007636:Keratoacanthoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D011493:Protein Kinase C / Q000378:metabolism; D012867:Skin / Q000378:metabolism; D012878:Skin Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015815:Cell Adhesion Molecules; D018797:Cell Cycle Proteins; C115084:Pard3 protein, mouse; C115015:PKC-3 protein; D011493:Protein Kinase C