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Two-Pore Channel Function Is Crucial for the Migration of Invasive Cancer Cells.
Nguyen, Ong Nam Phuong; Grimm, Christian; Schneider, Lina S; Chao, Yu-Kai; Atzberger, Carina; Bartel, Karin; Watermann, Anna; Ulrich, Melanie; Mayr, Doris; Wahl-Schott, Christian; Biel, Martin; Vollmar, Angelika M.
Afiliación
  • Nguyen ON; Department of Pharmacy, Pharmaceutical Biology, Ludwig-Maximilians-University Munich, Munich, Germany.
  • Grimm C; Department of Pharmacy, Center for Drug Research and Center for Integrated Protein Science Munich (CIPSM), Ludwig-Maximilians-University Munich, Munich, Germany.
  • Schneider LS; Department of Pharmacy, Pharmaceutical Biology, Ludwig-Maximilians-University Munich, Munich, Germany.
  • Chao YK; Department of Pharmacy, Center for Drug Research and Center for Integrated Protein Science Munich (CIPSM), Ludwig-Maximilians-University Munich, Munich, Germany.
  • Atzberger C; Department of Pharmacy, Pharmaceutical Biology, Ludwig-Maximilians-University Munich, Munich, Germany.
  • Bartel K; Department of Pharmacy, Pharmaceutical Biology, Ludwig-Maximilians-University Munich, Munich, Germany.
  • Watermann A; Department of Pharmacy, Pharmaceutical Biology, Ludwig-Maximilians-University Munich, Munich, Germany.
  • Ulrich M; Department of Pharmacy, Pharmaceutical Biology, Ludwig-Maximilians-University Munich, Munich, Germany.
  • Mayr D; Pathological Institute, Ludwig-Maximilians-University Munich, Munich, Germany.
  • Wahl-Schott C; Department of Pharmacy, Center for Drug Research and Center for Integrated Protein Science Munich (CIPSM), Ludwig-Maximilians-University Munich, Munich, Germany.
  • Biel M; Department of Pharmacy, Center for Drug Research and Center for Integrated Protein Science Munich (CIPSM), Ludwig-Maximilians-University Munich, Munich, Germany. angelika.vollmar@cup.uni-muenchen.de martin.biel@cup.uni-muenchen.de.
  • Vollmar AM; Department of Pharmacy, Pharmaceutical Biology, Ludwig-Maximilians-University Munich, Munich, Germany. angelika.vollmar@cup.uni-muenchen.de martin.biel@cup.uni-muenchen.de.
Cancer Res ; 77(6): 1427-1438, 2017 03 15.
Article en En | MEDLINE | ID: mdl-28108508
Metastatic invasion is the major cause of cancer-related deaths. In this study, we introduce two-pore channels (TPC), a recently described class of NAADP- and PI(3,5)P2-sensitive Ca2+-permeable cation channels in the endolysosomal system of cells, as candidate targets for the treatment of invasive cancers. Inhibition of the channel abrogated migration of metastatic cancer cells in vitro Silencing or pharmacologic inhibition of the two-pore channel TPC2 reduced lung metastasis of mammary mouse cancer cells. Disrupting TPC function halted trafficking of ß1-integrin, leading to its accumulation in EEA1-positive early endosomes. As a consequence, invasive cancer cells were no longer able to form leading edges, which are required for adequate migration. Our findings link TPC to cancer cell migration and provide a preclinical proof of concept for their candidacy as targets to treat metastatic cancers. Cancer Res; 77(6); 1427-38. ©2017 AACR.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Canales de Calcio / Neoplasias Mamarias Animales / Movimiento Celular / Calcio / Neoplasias Pulmonares / NADP Límite: Animals Idioma: En Revista: Cancer Res Año: 2017 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Estados Unidos
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Canales de Calcio / Neoplasias Mamarias Animales / Movimiento Celular / Calcio / Neoplasias Pulmonares / NADP Límite: Animals Idioma: En Revista: Cancer Res Año: 2017 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Estados Unidos