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The DUBA-SLC7A11-c-Myc axis is critical for stemness and ferroptosis.
Wang, Zuli; Ouyang, Lianlian; Liu, Na; Li, Tiansheng; Yan, Bokang; Mao, Chao; Xiao, Desheng; Gan, Boyi; Liu, Shuang; Tao, Yongguang.
Afiliación
  • Wang Z; Center for Tissue Engineering and Stem Cell Research, Guizhou Medical University, Guiyang, Guizhou, 550025, China.
  • Ouyang L; Department of Pathology, Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Xiangya Hospital, Central South University, Changsha, Hunan, 410078, China.
  • Liu N; NHC Key Laboratory of Carcinogenesis of Ministry of Health (Central South University), Cancer Research Institute, School of Basic Medicine, Central South University, Changsha, Hunan, 410078, China.
  • Li T; Department of Pathology, Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Xiangya Hospital, Central South University, Changsha, Hunan, 410078, China.
  • Yan B; NHC Key Laboratory of Carcinogenesis of Ministry of Health (Central South University), Cancer Research Institute, School of Basic Medicine, Central South University, Changsha, Hunan, 410078, China.
  • Mao C; Department of Pathology, Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Xiangya Hospital, Central South University, Changsha, Hunan, 410078, China.
  • Xiao D; NHC Key Laboratory of Carcinogenesis of Ministry of Health (Central South University), Cancer Research Institute, School of Basic Medicine, Central South University, Changsha, Hunan, 410078, China.
  • Gan B; Department of Pathology, Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Xiangya Hospital, Central South University, Changsha, Hunan, 410078, China.
  • Liu S; NHC Key Laboratory of Carcinogenesis of Ministry of Health (Central South University), Cancer Research Institute, School of Basic Medicine, Central South University, Changsha, Hunan, 410078, China.
  • Tao Y; Department of Pathology, Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Xiangya Hospital, Central South University, Changsha, Hunan, 410078, China.
Oncogene ; 42(36): 2688-2700, 2023 09.
Article en En | MEDLINE | ID: mdl-37537342
Ferroptosis is characterized by the accumulation of lipid peroxidation as a unique iron-dependent cell death. However, the interplay between stemness and ferroptosis remains unknown. Here, we demonstrate that undifferentiated cells are more sensitive to ferroptosis than differentiated cells, and cystine transporter SLC7A11 protein is highly up-regulated by deubiquitinase DUBA in differentiated cells. Additionally, DUBA promotes stemness by deubiquitinating SLC7A11. Moreover, SLC7A11 drastically increases the expression of c-Myc through cysteine, the combination of sorafenib and c-Myc inhibitor EN4 has a synergetic effect on cancer therapy. Together, our results reveal that enhanced stemness increases the susceptibility to ferroptosis, and the DUBA-SLC7A11-c-Myc axis is pivotal for differentiated cancer stem cells (CSCs) resistant to ferroptosis, providing a promised targets to eradicate CSCs through ferroptosis.
Asunto(s)

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Ferroptosis Límite: Humans Idioma: En Revista: Oncogene Asunto de la revista: BIOLOGIA MOLECULAR / NEOPLASIAS Año: 2023 Tipo del documento: Article País de afiliación: China

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Ferroptosis Límite: Humans Idioma: En Revista: Oncogene Asunto de la revista: BIOLOGIA MOLECULAR / NEOPLASIAS Año: 2023 Tipo del documento: Article País de afiliación: China