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Article: Carnitine palmitoyltransferase 1C promotes cell survival and tumor growth under conditions of metabolic stress

TitleCarnitine palmitoyltransferase 1C promotes cell survival and tumor growth under conditions of metabolic stress
Authors
KeywordsCpt1C
Metabolic stress
Fatty acid homeostasis
Xenograft tumors
Rapamycin resistance
Issue Date2011
Citation
Genes and Development, 2011, v. 25, n. 10, p. 1041-1051 How to Cite?
AbstractTumor cells gain a survival/growth advantage by adapting their metabolism to respond to environmental stress, a process known as metabolic transformation. The best-known aspect of metabolic transformation is the Warburg effect, whereby cancer cells up-regulate glycolysis under aerobic conditions. However, other mechanisms mediating metabolic transformation remain undefined. Here we report that carnitine palmitoyltransferase 1C (CPT1C), a brain-specific metabolic enzyme, may participate in metabolic transformation. CPT1C expression correlates inversely with mammalian target of rapamycin (mTOR) pathway activation, contributes to rapamycin resistance in murine primary tumors, and is frequently up-regulated in human lung tumors. Tumor cells constitutively expressing CPT1C show increased fatty acid (FA) oxidation, ATP production, and resistance to glucose deprivation or hypoxia. Conversely, cancer cells lacking CPT1C produce less ATP and are more sensitive to metabolic stress. CPT1C depletion via siRNA suppresses xenograft tumor growth and metformin responsiveness in vivo. CPT1C can be induced by hypoxia or glucose deprivation and is regulated by AMPKa. Cpt1c-deficient murine embryonic stem (ES) cells show sensitivity to hypoxia and glucose deprivation and altered FA homeostasis. Our results indicate that cells can use a novel mechanism involving CPT1C and FA metabolism to protect against metabolic stress. CPT1C may thus be a new therapeutic target for the treatment of hypoxic tumors.
Persistent Identifierhttp://hdl.handle.net/10722/292634
ISSN
2023 Impact Factor: 7.5
2023 SCImago Journal Rankings: 5.015
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorZaugg, Kathrin-
dc.contributor.authorYao, Yi-
dc.contributor.authorReilly, Patrick T.-
dc.contributor.authorKannan, Karuppiah-
dc.contributor.authorKiarash, Reza-
dc.contributor.authorMason, Jacqueline-
dc.contributor.authorHuang, Ping-
dc.contributor.authorSawyer, Suzanne K.-
dc.contributor.authorFuerth, Benjamin-
dc.contributor.authorFaubert, Brandon-
dc.contributor.authorKalliomäki, Tuula-
dc.contributor.authorElia, Andrew-
dc.contributor.authorLuo, Xunyi-
dc.contributor.authorNadeem, Vincent-
dc.contributor.authorBungard, David-
dc.contributor.authorYalavarthi, Sirseesha-
dc.contributor.authorGrowney, Joseph D.-
dc.contributor.authorWakeham, Andrew-
dc.contributor.authorMoolani, Yasmin-
dc.contributor.authorSilvester, Jennifer-
dc.contributor.authorTen, Annick You-
dc.contributor.authorBakker, Walbert-
dc.contributor.authorTsuchihara, Katsuya-
dc.contributor.authorBerger, Shelley L.-
dc.contributor.authorHill, Richard P.-
dc.contributor.authorJones, Russell G.-
dc.contributor.authorTsao, Ming-
dc.contributor.authorRobinson, Murray O.-
dc.contributor.authorThompson, Craig B.-
dc.contributor.authorPan, Guohua-
dc.contributor.authorMak, Tak W.-
dc.date.accessioned2020-11-17T14:56:53Z-
dc.date.available2020-11-17T14:56:53Z-
dc.date.issued2011-
dc.identifier.citationGenes and Development, 2011, v. 25, n. 10, p. 1041-1051-
dc.identifier.issn0890-9369-
dc.identifier.urihttp://hdl.handle.net/10722/292634-
dc.description.abstractTumor cells gain a survival/growth advantage by adapting their metabolism to respond to environmental stress, a process known as metabolic transformation. The best-known aspect of metabolic transformation is the Warburg effect, whereby cancer cells up-regulate glycolysis under aerobic conditions. However, other mechanisms mediating metabolic transformation remain undefined. Here we report that carnitine palmitoyltransferase 1C (CPT1C), a brain-specific metabolic enzyme, may participate in metabolic transformation. CPT1C expression correlates inversely with mammalian target of rapamycin (mTOR) pathway activation, contributes to rapamycin resistance in murine primary tumors, and is frequently up-regulated in human lung tumors. Tumor cells constitutively expressing CPT1C show increased fatty acid (FA) oxidation, ATP production, and resistance to glucose deprivation or hypoxia. Conversely, cancer cells lacking CPT1C produce less ATP and are more sensitive to metabolic stress. CPT1C depletion via siRNA suppresses xenograft tumor growth and metformin responsiveness in vivo. CPT1C can be induced by hypoxia or glucose deprivation and is regulated by AMPKa. Cpt1c-deficient murine embryonic stem (ES) cells show sensitivity to hypoxia and glucose deprivation and altered FA homeostasis. Our results indicate that cells can use a novel mechanism involving CPT1C and FA metabolism to protect against metabolic stress. CPT1C may thus be a new therapeutic target for the treatment of hypoxic tumors.-
dc.languageeng-
dc.relation.ispartofGenes and Development-
dc.subjectCpt1C-
dc.subjectMetabolic stress-
dc.subjectFatty acid homeostasis-
dc.subjectXenograft tumors-
dc.subjectRapamycin resistance-
dc.titleCarnitine palmitoyltransferase 1C promotes cell survival and tumor growth under conditions of metabolic stress-
dc.typeArticle-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1101/gad.1987211-
dc.identifier.pmid21576264-
dc.identifier.pmcidPMC3093120-
dc.identifier.scopuseid_2-s2.0-79956326256-
dc.identifier.volume25-
dc.identifier.issue10-
dc.identifier.spage1041-
dc.identifier.epage1051-
dc.identifier.eissn1549-5477-
dc.identifier.isiWOS:000290611800007-
dc.identifier.issnl0890-9369-

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