Lung cancer is the leading cause of deaths in United States and non-small cell lung cancer (NSCLC) accounts for ∼85% of all lung cancers with a 5-year survival rate of approximately ∼16%. Therefore there is an immediate need to develop new strategies for early detection and more effective treatments options. Mitochondrial dysfunction including but not limited to defects in mitochondrial genomics and dynamics has long been implicated to play a role in human health and disease particularly in cancer initiation, progression and treatment options since it plays a pivotal role in cell death and survival. Lysocardiolipin acyltransferase (LYCAT), a Cardiolipin remodeling enzyme regulating the 18:2 linoleic acid pattern of mammalian mitochondrial cardiolipin, plays a crucial role in maintaining normal mitochondrial function and vascular development. LYCAT was shown to be up-regulated in cancers; however, the role of LYCAT in lung cancer is yet unclear. Probing the protein expression of LYCAT in lung cancer specimens, non-transformed bronchial epithelial cell lines and 5 lung cancer cell lines revealed increased LYCAT expression and activity in all the lung cancer samples and cell lines tested in comparison to the control lung tissues and non-transformed epithelial cell lines. To determine the role of LYCAT in lung cancer, NSCLC cell lines H2122 and H23 were transfected with either scrambled or LYCAT shRNA and differences in serum-induced cell proliferation, migration, clonogenecity and mitochondrial dynamics were determined. Our results demonstrated that down-regulation of LYCAT by shRNA significantly attenuated cell migration, proliferation, and invasion in NSCLC cell lines compared to control cell lines. Furthermore knockdown of LYCAT expression in NSCLC cell lines inhibited mitochondrial fragmentation and enhanced mitochondrial fusion. Taken together, these data demonstrate a strong association between increased LYCAT expression and cell proliferation, motility, invasion and mitochondrial dynamics in NSCLC cells. Thus, development of targeted therapies to reduce LYCAT expression in NSCLC should be beneficial. This work in part was supported by funds from the College of Medicine, UIC and NIH HL98050 to VN.
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