Abstract
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.
Highlights
Many molecular targets have been identified to improve the treatment strategies in non-small cell lung cancer (NSCLC), 5-year overall survival rate for patients with NSCLC is still 16% [1]
We tested the association between xCT protein expression by immunohistochemistry and clinical outcomes in tissue microarrays built in the laboratory and representing a total of 254 NSCLCs (Table 1)
Accumulating evidence demonstrated that xCT plays an important role in the development and the survival of different cancer cell types including breast, glioma, and lymphoma [16, 32,33,34]
Summary
Many molecular targets have been identified to improve the treatment strategies in non-small cell lung cancer (NSCLC), 5-year overall survival rate for patients with NSCLC is still 16% [1]. A subgroup of tumors has been found to be driven by genetic alterations in NSCLC, such as EGFR mutations and ALK rearrangements. Tumors with these targetable oncogenic alterations tend to respond to EGFR or ALK inhibitors [2,3,4]. The determinants of tumor progression complicated by the tremendous heterogeneity in molecular alterations in lung cancer are only partially understood.
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