Glutathione S-transferase A1 mediates nicotine-induced lung cancer cell metastasis by promoting epithelial-mesenchymal transition

Abstract

Abstract. The present study aimed to investigate the effect of glutathione S-transferase A1 (GSTA1) on lung cancer cell viability, invasion and adhesion in the presence of nicotine in vitro. Furthermore, the effect of GSTA1 on the epithelial-mesenchymal transition (EMT), a process strongly associated with lung cancer metastasis, was examined. Human lung carcinoma A549 cells were treated with various concentrations of nicotine (0.01, 0.1, 1 and 10 µM) and levels of GSTA1 mRNA and protein were measured by reverse transcription-quantitative polymerase chain reaction and western blot analysis, respectively. To knock down GSTA1 expression, GSTA1-small interfering RNA was transfected into A549 cells. Cell viability, invasion and adhesion abilities were determined by MTT, Transwell-Matrigel invasion and cell adhesion assays, respectively. The expression of the epithelial cell markers E-cadherin and keratin, and the mesenchymal cell markers vimentin and N-cadherin in A549 cells were examined by western blot analysis. The current study indicated that the expression of GSTA1 was increased in A549 cells following nicotine treatment. GSTA1 suppression inhibited the viability, invasion and adhesion of lung cancer cells. In addition, the increase in lung cancer cell viability, invasion and adhesion by nicotine was suppressed following GSTA1 knockdown. Furthermore, GSTA1 affected the expression of EMT markers in nicotine-treated or untreated lung cancer cells. Thus the present study demonstrates that GSTA1 promotes lung cancer cell invasion and adhesion and mediates the effect of nicotine on lung cancer cell metastasis in vitro. Furthermore, the results demonstrated that GSTA1 exerts its effect on lung cancer cell metastasis by promoting the EMT. IntroductionGlobally, lung cancer is the leading cause of cancer-associated mortality in men and the second leading cause of cancer-associated mortality in women (1). Recurrence and metastasis are the biggest obstacles to effective lung cancer treatment. Although treatments for lung cancer have improved over the past few decades, the 5-year survival rate is only ~16% (2). Thus, it is important to identify biomarkers associated with lung cancer metastasis in order to improve the therapeutic strategies available.Tumor metastasis is a complex process consisting of multiple biological steps (3) including increased motility, invasion into surrounding tissue, intravasation, entry and survival in the circulation, extravasation and eventual colonization of a distant site (4-6). The epithelial-mesenchymal transition (EMT) is a well-coordinated process that induces metastasis in epithelial cancer (7,8). Glutathione S-transferase A 1 (GSTA1) is an isoform of GST primarily involved in the detoxification of electrophilic compounds by undergoing conjugation with glutathione (9,10). Previous studies have demonstrated that the altered expression of GST genes increases the risk of prostate cancer and hepatocellular carcinoma (11)(12)(13)(14). Recently, Pan et al (15) identified the potential of GSTA1...

Transcriptomic and computational analysis identified LPA metabolism, KLHL14 and KCNE3 as novel regulators of Epithelial-Mesenchymal Transition

“…Moreover, both genes are local hubs of mAEC network while GSTM3 is also a bottleneck, thus suggesting a driving role in the induction of EMT. In agreements with these results, GSTA1-1 and GSTM3 have been recognized as stimulatory respect proliferation, apoptosis evasion, metastatic process and EMT-related genes induction [52][53][54] .…”

Glutathione S-transferase A1 suppresses tumor progression and indicates better prognosis of human primary hepatocellular carcinoma

“…Eight isoforms of cytosolic-soluble GSTs have been recognized in humans, including α, κ, μ, π, σ, θ, ζ, and ω 3,4 . Glutathione S-transferase α1 (GSTA1, Gene ID: 2938) has shown both stimulatory [5][6][7][8] and inhibitory effects [9][10][11][12] on tumorigenesis. The association between genetic polymorphism of GSTA1 and susceptibility to cancer has been discussed in previous studies [13][14][15] , but…”

The Expression of E-Cadherin and Vimentin in Non-Small-Cell Lung Cancer and Their Correlation with Epithelial-Mesenchymal Transition (EMT)

“…Meanwhile, Dasgupta P et al [18] showed nicotine, an active component of cigarettes, had been found to cause down-regulation of E-cadherin and up-regulation of Vimentin in lung cancer cell line A549 in vitro. The aged, smoking male tend to suffer lung squamous carcinoma from the standpoint of clinical medicine.…”