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Mutant p53 regulates ovarian cancer transformed phenotypes through autocrine matrix deposition.
Iwanicki, Marcin P; Chen, Hsing-Yu; Iavarone, Claudia; Zervantonakis, Ioannis K; Muranen, Taru; Novak, Marián; Ince, Tan A; Drapkin, Ronny; Brugge, Joan S.
Afiliación
  • Iwanicki MP; Department of Cell Biology, Harvard Medical School, Boston, Massachusetts, USA.
  • Chen HY; Department of Cell Biology, Harvard Medical School, Boston, Massachusetts, USA.
  • Iavarone C; Department of Cell Biology, Harvard Medical School, Boston, Massachusetts, USA.
  • Zervantonakis IK; Department of Cell Biology, Harvard Medical School, Boston, Massachusetts, USA.
  • Muranen T; Department of Cell Biology, Harvard Medical School, Boston, Massachusetts, USA.
  • Novak M; Dana-Farber Cancer Institute, Department of Medical Oncology, Center for Molecular Oncologic Pathology, Boston, Massachusetts, USA.
  • Ince TA; Stem Cell Institute, University of Miami Miller School of Medicine, Miami, Florida, USA.
  • Drapkin R; Dana-Farber Cancer Institute, Department of Medical Oncology, Center for Molecular Oncologic Pathology, Boston, Massachusetts, USA.
  • Brugge JS; Penn Ovarian Cancer Research Center, Basser Center for BRCA, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
JCI Insight ; 1(10)2016 Jul 07.
Article en En | MEDLINE | ID: mdl-27482544
High-grade serous ovarian carcinoma (HGS-OvCa) harbors p53 mutations and can originate from the epithelial cell compartment of the fallopian tube fimbriae. From this site, neoplastic cells detach, survive in the peritoneal cavity, and form cellular clusters that intercalate into the mesothelium to form ovarian and peritoneal masses. To examine the contribution of mutant p53 to phenotypic alterations associated with HGS-OvCA, we developed live-cell microscopy assays that recapitulate these early events in cultured fallopian tube nonciliated epithelial (FNE) cells. Expression of stabilizing mutant variants of p53, but not depletion of endogenous wild-type p53, in FNE cells promoted survival and cell-cell aggregation under conditions of cell detachment, leading to the formation of cell clusters with mesothelium-intercalation capacity. Mutant p53R175H-induced phenotypes were dependent on fibronectin production, α5ß1 fibronectin receptor engagement, and TWIST1 expression. These results indicate that FNE cells expressing stabilizing p53 mutants acquire anchorage independence and subsequent mesothelial intercalation capacity through a mechanism involving mesenchymal transition and matrix production. These findings provide important new insights into activities of mutant p53 in the cells of origin of HGS-OvCa.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: JCI Insight Año: 2016 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: JCI Insight Año: 2016 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos