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

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 i...

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Published in:Nature communications 2022-08, Vol.13 (1), p.4554-16, Article 4554
Main Authors: Tan, Yuying, Li, Junjie, Zhao, Guangyuan, Huang, Kai-Chih, Cardenas, Horacio, Wang, Yinu, Matei, Daniela, Cheng, Ji-Xin
Format: Article
Language:English
Subjects:
14/19
14/34
140/133
38
38/109
45/77
631/1647/245/2226
631/67/1059/2326
631/67/2327
64/60
Antineoplastic Agents - pharmacology
Antineoplastic Agents - therapeutic use
Cancer
Carboplatin
Cell Line, Tumor
Cell survival
Chemoresistance
Chemotherapy
Cisplatin
Cisplatin - pharmacology
Cisplatin - therapeutic use
Drug Resistance, Neoplasm
Energy metabolism
Fatty acids
Fatty Acids - pharmacology
Female
Glucose
Glucose - metabolism
Glycolysis
Humanities and Social Sciences
Humans
In vivo methods and tests
Lipogenesis
Metabolism
multidisciplinary
Ovarian cancer
Ovarian Neoplasms - pathology
Oxidation
Oxidation resistance
Oxidative stress
Platinum
Platinum - pharmacology
Raman spectra
Science
Science (multidisciplinary)
Tumor cell lines
Tumors
Xenografts
Xenotransplantation
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container_title Nature communications
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creator Tan, Yuying
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Zhao, Guangyuan
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Cheng, Ji-Xin
description 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. Metabolic reprogramming is associated with cancer initiation, progression and resistance to therapy. Here, the authors show that metabolic reprogramming from glycolysis to fatty acid uptake and beta-oxidation is associated with cancer-cell platinum-based chemotherapy resistance.
doi_str_mv 10.1038/s41467-022-32101-w
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subjects 14/19
14/34
140/133
38
38/109
45/77
631/1647/245/2226
631/67/1059/2326
631/67/2327
64/60
Antineoplastic Agents - pharmacology
Antineoplastic Agents - therapeutic use
Cancer
Carboplatin
Cell Line, Tumor
Cell survival
Chemoresistance
Chemotherapy
Cisplatin
Cisplatin - pharmacology
Cisplatin - therapeutic use
Drug Resistance, Neoplasm
Energy metabolism
Fatty acids
Fatty Acids - pharmacology
Female
Glucose
Glucose - metabolism
Glycolysis
Humanities and Social Sciences
Humans
In vivo methods and tests
Lipogenesis
Metabolism
multidisciplinary
Ovarian cancer
Ovarian Neoplasms - pathology
Oxidation
Oxidation resistance
Oxidative stress
Platinum
Platinum - pharmacology
Raman spectra
Science
Science (multidisciplinary)
Tumor cell lines
Tumors
Xenografts
Xenotransplantation
title Metabolic reprogramming from glycolysis to fatty acid uptake and beta-oxidation in platinum-resistant cancer cells
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