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TRPV4 Regulates Breast Cancer Cell Extravasation, Stiffness and Actin Cortex.
Lee, Wen Hsin; Choong, Lee Yee; Mon, Naing Naing; Lu, SsuYi; Lin, Qingsong; Pang, Brendan; Yan, Benedict; Krishna, Vedula Sri Ram; Singh, Himanshu; Tan, Tuan Zea; Thiery, Jean Paul; Lim, Chwee Teck; Tan, Patrick Boon Ooi; Johansson, Martin; Harteneck, Christian; Lim, Yoon Pin.
Afiliación
  • Lee WH; Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
  • Choong LY; Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
  • Mon NN; Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
  • Lu S; Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
  • Lin Q; Department of Biological Sciences, Faculty of Science, National University of Singapore, Singapore.
  • Pang B; Cancer Science Institute of Singapore, Singapore.
  • Yan B; National University Hospital, Department of Laboratory Medicine, Singapore.
  • Krishna VS; Mechanobiology Institute, National University of Singapore, Singapore.
  • Singh H; Department of Biomedical Engineering, National University of Singapore, Singapore.
  • Tan TZ; Cancer Science Institute of Singapore, Singapore.
  • Thiery JP; Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
  • Lim CT; Cancer Science Institute of Singapore, Singapore.
  • Tan PB; Mechanobiology Institute, National University of Singapore, Singapore.
  • Johansson M; Department of Biomedical Engineering, National University of Singapore, Singapore.
  • Harteneck C; Duke-NUS Graduate Medical School, Singapore.
  • Lim YP; Respiratorius AB, Lund, Sweden.
Sci Rep ; 6: 27903, 2016 06 13.
Article en En | MEDLINE | ID: mdl-27291497
Metastasis is a significant health issue. The standard mode of care is combination of chemotherapy and targeted therapeutics but the 5-year survival rate remains low. New/better drug targets that can improve outcomes of patients with metastatic disease are needed. Metastasis is a complex process, with each step conferred by a set of genetic aberrations. Mapping the molecular changes associated with metastasis improves our understanding of the etiology of this disease and contributes to the pipeline of targeted therapeutics. Here, phosphoproteomics of a xenograft-derived in vitro model comprising 4 isogenic cell lines with increasing metastatic potential implicated Transient Receptor Potential Vanilloid subtype 4 in breast cancer metastasis. TRPV4 mRNA levels in breast, gastric and ovarian cancers correlated with poor clinical outcomes, suggesting a wide role of TRPV4 in human epithelial cancers. TRPV4 was shown to be required for breast cancer cell invasion and transendothelial migration but not growth/proliferation. Knockdown of Trpv4 significantly reduced the number of metastatic nodules in mouse xenografts leaving the size unaffected. Overexpression of TRPV4 promoted breast cancer cell softness, blebbing, and actin reorganization. The findings provide new insights into the role of TRPV4 in cancer extravasation putatively by reducing cell rigidity through controlling the cytoskeleton at the cell cortex.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Citoesqueleto de Actina / Neoplasias de la Mama / Canales Catiónicos TRPV Tipo de estudio: Prognostic_studies Límite: Animals / Female / Humans Idioma: En Revista: Sci Rep Año: 2016 Tipo del documento: Article País de afiliación: Singapur Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Citoesqueleto de Actina / Neoplasias de la Mama / Canales Catiónicos TRPV Tipo de estudio: Prognostic_studies Límite: Animals / Female / Humans Idioma: En Revista: Sci Rep Año: 2016 Tipo del documento: Article País de afiliación: Singapur Pais de publicación: Reino Unido