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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • 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

Published Date

  • September 2018

Published In

Volume / Issue

  • 37 / 36

Start / End Page

  • 5007 - 5019

PubMed ID

  • 29789716

Pubmed Central ID

  • 29789716

Electronic International Standard Serial Number (EISSN)

  • 1476-5594

International Standard Serial Number (ISSN)

  • 0950-9232

Digital Object Identifier (DOI)

  • 10.1038/s41388-018-0307-z

Language

  • eng