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Metabolic reprogramming from glycolysis to fatty acid uptake and beta-oxidation in platinum-resistant cancer cells

Author

Listed:
  • Yuying Tan

    (Boston University)

  • Junjie Li

    (Boston University)

  • Guangyuan Zhao

    (Northwestern University)

  • Kai-Chih Huang

    (Boston University)

  • Horacio Cardenas

    (Northwestern University)

  • Yinu Wang

    (Northwestern University)

  • Daniela Matei

    (Northwestern University
    Robert H. Lurie Comprehensive Cancer Center)

  • Ji-Xin Cheng

    (Boston University
    Boston University
    Boston University)

Abstract

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.

Suggested Citation

  • Yuying Tan & Junjie Li & Guangyuan Zhao & Kai-Chih Huang & Horacio Cardenas & Yinu Wang & Daniela Matei & Ji-Xin Cheng, 2022. "Metabolic reprogramming from glycolysis to fatty acid uptake and beta-oxidation in platinum-resistant cancer cells," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-32101-w
    DOI: 10.1038/s41467-022-32101-w
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