Lysocardiolipin acyltransferase regulates NSCLC cell proliferation and migration by modulating mitochondrial dynamics.
| Autor: | Huang LS; Department of Pharmacology, University of Illinois, Chicago, Illinois, USA., Kotha SR; Department of Pharmacology, University of Illinois, Chicago, Illinois, USA., Avasarala S; Department of Medicine, University of Illinois, Chicago, Illinois, USA., VanScoyk M; Department of Medicine, University of Illinois, Chicago, Illinois, USA., Winn RA; Massey Cancer Center, Virginia Commonwealth University, Richmond, Virginia, USA., Pennathur A; Department of Cardiothoracic Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA., Yashaswini PS; Department of Pharmacology, University of Illinois, Chicago, Illinois, USA., Bandela M; Department of Medicine, University of Illinois, Chicago, Illinois, USA., Salgia R; Beckman Research Institute, City of Hope, Los Angeles, California, USA., Tyurina YY; Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA., Kagan VE; Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA; Department of Chemistry, Pharmacology, and Chemical Biology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA; Laboratory of Navigational Redox Lipidomics, I. M. Sechenov Moscow State Medical University, Moscow, Russia., Zhu X; Center for Cardiovascular Research and Department of Emergency Medicine, University of Illinois, Chicago, Illinois, USA., Reddy SP; Department of Pediatrics, University of Illinois, Chicago, Illinois, USA., Sudhadevi T; Department of Pediatrics, University of Illinois, Chicago, Illinois, USA., Punathil-Kannan PK; Department of Pharmacology, University of Illinois, Chicago, Illinois, USA., Harijith A; Department of Pediatrics, University of Illinois, Chicago, Illinois, USA., Ramchandran R; Department of Pharmacology, University of Illinois, Chicago, Illinois, USA., Bikkavilli RK; Department of Medicine, University of Illinois, Chicago, Illinois, USA. Electronic address: kamesh@uic.edu., Natarajan V; Department of Pharmacology, University of Illinois, Chicago, Illinois, USA; Department of Medicine, University of Illinois, Chicago, Illinois, USA. Electronic address: visnatar@uic.edu. |
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| Jazyk: | angličtina |
| Zdroj: | The Journal of biological chemistry [J Biol Chem] 2020 Sep 18; Vol. 295 (38), pp. 13393-13406. Date of Electronic Publication: 2020 Jul 30. |
| DOI: | 10.1074/jbc.RA120.012680 |
| Abstrakt: | Lysocardiolipin acyltransferase (LYCAT), a cardiolipin (CL)-remodeling enzyme, is crucial for maintaining normal mitochondrial function and vascular development. Despite the well-characterized role for LYCAT in the regulation of mitochondrial dynamics, its involvement in lung cancer, if any, remains incompletely understood. In this study, in silico analysis of TCGA lung cancer data sets revealed a significant increase in LYCAT expression, which was later corroborated in human lung cancer tissues and immortalized lung cancer cell lines via indirect immunofluorescence and immunoblotting, respectively. Stable knockdown of LYCAT in NSCLC cell lines not only reduced CL and increased monolyso-CL levels but also reduced in vivo tumor growth, as determined by xenograft studies in athymic nude mice. Furthermore, blocking LYCAT activity using a LYCAT mimetic peptide attenuated cell migration, suggesting a novel role for LYCAT activity in promoting NSCLC. Mechanistically, the pro-proliferative effects of LYCAT were mediated by an increase in mitochondrial fusion and a G Competing Interests: Conflict of interest—The authors declare that they have no conflicts of interest with the contents of this article. (© 2020 Huang et al.) |
| Databáze: | MEDLINE |
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