Cellular transformation by cigarette smoke extract involves alteration of glycolysis and mitochondrial function in esophageal epithelial cells

Myoung Sook Kim, Yiping Huang, Juna Lee, Xiaoli Zhong, Wei Wen Jiang, Edward A. Ratovitski, David Sidransky

Research output: Contribution to journalArticlepeer-review

Abstract

Cigarette-smoking increases the risk of developing various types of human cancers including esophageal cancers. To test the effects of chronic cigarette smoke exposure directly on esophageal epithelium, cellular resistance to mainstream extract (MSE), or sidestream smoke extract (SSE) was developed in chronically exposed nonmalignant Het-1A cells. Anchorage-independent growth, in vitro invasion capacity and proliferation of the resistant cells increased compared with the unexposed, sensitive cells. An epithelial marker E-cadherin was down-regulated and mesenchymal markers N-cadherin and vimentin were up-regulated in the resistant cells. Het-1A cells resistant to MSE or SSE consumed more glucose, and produced more lactate than the sensitive cells. The increased anchorage-independent cell growth of the resistant cells was suppressed by a glycolysis inhibitor, 2-deoxy-D-glucose, indicating that these cells are highly dependent on the glycolytic pathway for survival. Decreased mitochondrial membrane potential and ATP production in the resistant cells indicate the presence of mitochondrial dysfunction induced by chronic exposure of cigarette smoke extract. Increased expression of nuclear genes in the glycolytic pathway and decreased levels of mitochondrial genes in the resistant cells support the notion that cigarette smoking significantly contributes to the transformation of nonmalignant esophageal epithelial cells into a tumorigenic phenotype.

Original languageEnglish (US)
Pages (from-to)269-281
Number of pages13
JournalInternational Journal of Cancer
Volume127
Issue number2
DOIs
StatePublished - Jul 15 2010

Keywords

  • Cigarette smoke extract
  • Esophageal cancer
  • Glycolysis

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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