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Metabolic reprogramming from glycolysis to fatty acid uptake and beta-oxidation in platinum-resistant cancer cells.
Tan, Yuying; Li, Junjie; Zhao, Guangyuan; Huang, Kai-Chih; Cardenas, Horacio; Wang, Yinu; Matei, Daniela; Cheng, Ji-Xin.
Afiliación
  • Tan Y; Biomedical Engineering, Boston University, Boston, MA, 02155, USA.
  • Li J; Electrical and Computer Engineering, Boston University, Boston, MA, 02155, USA. junjiel168@gmail.com.
  • Zhao G; Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA.
  • Huang KC; Biomedical Engineering, Boston University, Boston, MA, 02155, USA.
  • Cardenas H; Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA.
  • Wang Y; Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA.
  • Matei D; Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA. daniela.matei@northwestern.edu.
  • Cheng JX; Robert H. Lurie Comprehensive Cancer Center, Chicago, IL, 60611, USA. daniela.matei@northwestern.edu.
Nat Commun ; 13(1): 4554, 2022 08 05.
Article en En | MEDLINE | ID: mdl-35931676
Increased glycolysis is considered as a hallmark of cancer. Yet, cancer cell metabolic reprograming during therapeutic resistance development is under-studied. Here, through high-throughput stimulated Raman scattering imaging and single cell analysis, we find that cisplatin-resistant cells exhibit increased fatty acids (FA) uptake, accompanied by decreased glucose uptake and lipogenesis, indicating reprogramming from glucose to FA dependent anabolic and energy metabolism. A metabolic index incorporating glucose derived anabolism and FA uptake correlates linearly to the level of cisplatin resistance in ovarian cancer (OC) cell lines and primary cells. The increased FA uptake facilitates cancer cell survival under cisplatin-induced oxidative stress by enhancing beta-oxidation. Consequently, blocking beta-oxidation by a small molecule inhibitor combined with cisplatin or carboplatin synergistically suppresses OC proliferation in vitro and growth of patient-derived xenografts in vivo. Collectively, these findings support a rapid detection method of cisplatin-resistance at single cell level and a strategy for treating cisplatin-resistant tumors.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Ováricas / Antineoplásicos Límite: Female / Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Ováricas / Antineoplásicos Límite: Female / Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido