xCT (SLC7A11)-mediated metabolic reprogramming promotes non-small cell lung cancer progression.

Ji X, Qian J, Rahman SMJ, Siska PJ, Zou Y, Harris BK, Hoeksema MD, Trenary IA, Heidi C, Eisenberg R, Rathmell JC, Young JD, Massion PP
Oncogene. 2018 37 (36): 5007-5019

PMID: 29789716 · PMCID: PMC6127081 · DOI:10.1038/s41388-018-0307-z

Many tumors increase uptake and dependence on glucose, cystine or glutamine. These basic observations on cancer cell metabolism have opened multiple new diagnostic and therapeutic avenues in cancer research. Recent studies demonstrated that smoking could induce the expression of xCT (SLC7A11) in oral cancer cells, suggesting that overexpression of xCT may support lung tumor progression. We hypothesized that overexpression of xCT occurs in lung cancer cells to satisfy the metabolic requirements for growth and survival. Our results demonstrated that 1) xCT was highly expressed at the cytoplasmic membrane in non-small cell lung cancer (NSCLC), 2) the expression of xCT was correlated with advanced stage and predicted a worse 5-year survival, 3) targeting xCT transport activity in xCT overexpressing NSCLC cells with sulfasalazine decreased cell proliferation and invasion in vitro and in vivo and 4) increased dependence on glutamine was observed in xCT overexpressed normal airway epithelial cells. These results suggested that xCT regulate metabolic requirements during lung cancer progression and be a potential therapeutic target in NSCLC.

MeSH Terms (19)

3T3 Cells A549 Cells Amino Acid Transport System y+ Animals Carcinoma, Non-Small-Cell Lung Cell Line Cell Line, Tumor Cell Proliferation Cell Survival Cystine Cytoplasm Disease Progression Female Glutamine Humans Lung Neoplasms Male Mice Middle Aged

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