Your browser doesn't support javascript.
loading
Aneuploid Cell Survival Relies upon Sphingolipid Homeostasis.
Tang, Yun-Chi; Yuwen, Hui; Wang, Kaiying; Bruno, Peter M; Bullock, Kevin; Deik, Amy; Santaguida, Stefano; Trakala, Marianna; Pfau, Sarah J; Zhong, Na; Huang, Tao; Wang, Lan; Clish, Clary B; Hemann, Michael T; Amon, Angelika.
Afiliación
  • Tang YC; The Key Laboratory of Stem Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences & Shanghai Jiao Tong University School of Medicine, Shanghai, China. yctang@sibs.ac.cn
  • Yuwen H; The Key Laboratory of Stem Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences & Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Wang K; Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences & Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Bruno PM; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts.
  • Bullock K; Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts.
  • Deik A; Metabolomics Platform, Broad Institute of MIT and Harvard, Cambridge, Massachusetts.
  • Santaguida S; Metabolomics Platform, Broad Institute of MIT and Harvard, Cambridge, Massachusetts.
  • Trakala M; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts.
  • Pfau SJ; Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts.
  • Zhong N; Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts.
  • Huang T; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts.
  • Wang L; Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts.
  • Clish CB; Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts.
  • Hemann MT; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts.
  • Amon A; Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts.
Cancer Res ; 77(19): 5272-5286, 2017 10 01.
Article en En | MEDLINE | ID: mdl-28775166
Aneuploidy, a hallmark of cancer cells, poses an appealing opportunity for cancer treatment and prevention strategies. Using a cell-based screen to identify small molecules that could selectively kill aneuploid cells, we identified the compound N-[2-hydroxy-1-(4-morpholinylmethyl)-2-phenylethyl]-decanamide monohydrochloride (DL-PDMP), an antagonist of UDP-glucose ceramide glucosyltransferase. DL-PDMP selectively inhibited proliferation of aneuploid primary mouse embryonic fibroblasts and aneuploid colorectal cancer cells. Its selective cytotoxic effects were based on further accentuating the elevated levels of ceramide, which characterize aneuploid cells, leading to increased apoptosis. We observed that DL-PDMP could also enhance the cytotoxic effects of paclitaxel, a standard-of-care chemotherapeutic agent that causes aneuploidy, in human colon cancer and mouse lymphoma cells. Our results offer pharmacologic evidence that the aneuploid state in cancer cells can be targeted selectively for therapeutic purposes, or for reducing the toxicity of taxane-based drug regimens. Cancer Res; 77(19); 5272-86. ©2017 AACR.
Asunto(s)
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Esfingolípidos / Neoplasias Colorrectales / Embrión de Mamíferos / Fibroblastos / Homeostasis / Aneuploidia / Linfoma Límite: Animals / Female / Humans / Male Idioma: En Revista: Cancer Res Año: 2017 Tipo del documento: Article País de afiliación: China 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 Asunto principal: Esfingolípidos / Neoplasias Colorrectales / Embrión de Mamíferos / Fibroblastos / Homeostasis / Aneuploidia / Linfoma Límite: Animals / Female / Humans / Male Idioma: En Revista: Cancer Res Año: 2017 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos