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Chromium contributes to human bronchial epithelial cell carcinogenesis by activating Gli2 and inhibiting autophagy

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Abstract

Occupational and environmental inhalation exposure to hexavalent chromium [Cr(VI)] compounds has been confirmed to cause respiratory system injury and cancer. The molecular mechanisms of chromium carcinogenesis still require further study. We established Cr(VI)-transformed cells (BEAS-2B-Cr) after chronic exposure of immortalized normal human bronchial epithelial BEAS-2B cells to low doses of Cr(VI), which obtained the ability of anchorage-independent growth. BEAS-2B-Cr cells not only exhibited stronger proliferation, migration, invasion and tumorigenesis capabilities but also acquired an altered and distinct Gli2 gene expression pattern compared with untreated parental BEAS-2B cells (P-NC) and the control BEAS-2B cells (NC). Interestingly, we found that activation of Gli2 by Cr(VI) treatment prevented the induction of autophagy. Using a gene silencing approach, we showed that Gli2 plays an important role in the malignant properties of BEAS-2B-Cr cells. Downregulation of Gli2 induced autophagy and inhibited cell proliferation and colony forming abilities, which are both upregulated in BEAS-2B-Cr cells compared to NC cells. In addition, inhibition of autophagy by 3-methyladenine (3-MA) partially suppressed the cytotoxicity induced by GANT61-induced inhibition of Gli2. These results demonstrate that hexavalent chromium Cr(VI) activates Gli2 to promote the proliferation of BEAS-2B-Cr cells by inhibition of autophagy, which contributes to human bronchial epithelial cell carcinogenesis. Gli2 may not only play an important role in lung cancer pathogenesis, but also be a promising early indicator in monitoring exposure to chromium.

Graphical abstract: Chromium contributes to human bronchial epithelial cell carcinogenesis by activating Gli2 and inhibiting autophagy

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Publication details

The article was received on 28 Sep 2016, accepted on 15 Feb 2017, published on 15 Feb 2017 and first published online on 15 Feb 2017


Article type: Paper
DOI: 10.1039/C6TX00372A
Citation: Toxicol. Res., 2017, Advance Article
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    Chromium contributes to human bronchial epithelial cell carcinogenesis by activating Gli2 and inhibiting autophagy

    J. Huang, G. Wu, R. Zeng, J. Wang, R. Cai, J. C. Ho, J. Zhang and Y. Zheng, Toxicol. Res., 2017, Advance Article , DOI: 10.1039/C6TX00372A

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