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Induction of non-apoptotic programmed cell death by oncogenic RAS in human epithelial cells and its suppression by MYC overexpression.
Dendo, Kasumi; Yugawa, Takashi; Nakahara, Tomomi; Ohno, Shin-Ichi; Goshima, Naoki; Arakawa, Hirofumi; Kiyono, Tohru.
Afiliación
  • Dendo K; Division of Carcinogenesis and Cancer Prevention, National Cancer Center Research Institute, Tsukiji, Chuo-ku, Tokyo, Japan.
  • Yugawa T; Department of NCC Cancer Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Yushima, Bunkyou-ku, Tokyo, Japan.
  • Nakahara T; Division of Carcinogenesis and Cancer Prevention, National Cancer Center Research Institute, Tsukiji, Chuo-ku, Tokyo, Japan.
  • Ohno SI; Division of Carcinogenesis and Cancer Prevention, National Cancer Center Research Institute, Tsukiji, Chuo-ku, Tokyo, Japan.
  • Goshima N; Division of Carcinogenesis and Cancer Prevention, National Cancer Center Research Institute, Tsukiji, Chuo-ku, Tokyo, Japan.
  • Arakawa H; Molecular Profiling Research Center for Drug Discovery, National Institute of Advanced Industrial Science and Technology, Aomi, Koto-ku, Tokyo, Japan.
  • Kiyono T; Department of NCC Cancer Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Yushima, Bunkyou-ku, Tokyo, Japan.
Carcinogenesis ; 39(2): 202-213, 2018 02 09.
Article en En | MEDLINE | ID: mdl-29106503
Oncogenic mutations of RAS genes, found in about 30% of human cancers, are considered to play important roles in cancer development. However, oncogenic RAS can also induce senescence in mouse and human normal fibroblasts. In some cell lines, oncogenic RAS has been reported to induce non-apoptotic programed cell death (PCD). Here, we investigated effects of oncogenic RAS expression in several types of normal human epithelial cells. Oncogenic RAS but not wild-type RAS stimulated macropinocytosis with accumulation of large-phase lucent vacuoles in the cytoplasm, subsequently leading to cell death which was indistinguishable from a recently proposed new type of PCD, methuosis. A RAC1 inhibitor suppressed accumulation of macropinosomes and overexpression of MYC attenuated oncogenic RAS-induced such accumulation, cell cycle arrest and cell death. MYC suppression or rapamycin treatment in some cancer cell lines harbouring oncogenic mutations in RAS genes induced cell death with accumulation of macropinosomes. These results suggest that this type of non-apoptotic PCD is a tumour-suppressing mechanism acting against oncogenic RAS mutations in normal human epithelial cells, which can be overcome by MYC overexpression, raising the possibility that its induction might be a novel approach to treatment of RAS-mutated human cancers.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas Proto-Oncogénicas c-myc / Muerte Celular / Proteínas ras / Células Epiteliales Límite: Humans Idioma: En Revista: Carcinogenesis Año: 2018 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas Proto-Oncogénicas c-myc / Muerte Celular / Proteínas ras / Células Epiteliales Límite: Humans Idioma: En Revista: Carcinogenesis Año: 2018 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Reino Unido