TASK‑1 induces gefitinib resistance by promoting cancer initiating cell formation and epithelial‑mesenchymal transition in lung cancer

Wang,Xing‑Guang; Yuan,Na‑Xin; Li,Xin‑Peng; Chen,Fang‑Fang

doi:10.3892/etm.2017.5426

TASK‑1 induces gefitinib resistance by promoting cancer initiating cell formation and epithelial‑mesenchymal transition in lung cancer

Authors:
- Xing‑Guang Wang
- Na‑Xin Yuan
- Xin‑Peng Li
- Fang‑Fang Chen
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Affiliations: Department of Respiratory Medicine, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China, Department of Respiratory Medicine, Dezhou People's Hospital, Dezhou, Shandong 253014, P.R. China, Department of Respiratory Medicine, Shandong Provincial Qianfoshan Hospital Affiliated to Shandong University, Jinan, Shandong 250014, P.R. China
Published online on: November 1, 2017 https://doi.org/10.3892/etm.2017.5426
Pages: 365-370

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Abstract

Cancer initiating cell (CIC) formation and epithelial‑mesenchymal transition (EMT) are pivotal events in lung cancer cell invasion and metastasis. They have been shown to occur in gefitinib resistance. Studying the molecular mechanisms of CICs, EMT and acquired gefitinib resistance will enhance the understanding of the pathogenesis and progression of the disease and offer novel targets for effective therapies. TWIK‑related acid‑sensitive K(+) (TASK‑1) is expressed in a subset of non‑small‑cell lung cancer (NSCLC) cell lines, where it promotes cell proliferation while inhibiting apoptosis. In the present study, TASK‑1 was demonstrated to induce gefitinib resistance in the A549 NSCLC cell line. Overexpression of TASK‑1 promoted the acquisition of CIC‑like traits by A549 cells. CD133, octamer‑binding transcription factor 4 (OCT‑4) and Nanog have been suggested to be markers of CICs in lung cancer. It was demonstrated that overexpression of TASK‑1 promoted CD133, OCT‑4 and Nanog protein expression in A549 cells. Increased formation of stem cell‑like populations results in EMT of cancer cells. The present study found that overexpression of TASK‑1 promoted EMT of A549 cells. Thus, downregulation of TASK‑1 may represent a novel strategy for EMT reversal, decreasing CIC‑like traits and increasing gefitinib sensitivity of NSCLCs.

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