An Autocrine IL-6/IGF-1R Loop Mediates EMT and Promotes Tumor Growth in Non-small Cell Lung Cancer

Zheng, Xianan; Lu, Guohua; Yao, Yinan; Gu, Wei

doi:10.7150/ijbs.31999

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Int J Biol Sci 2019; 15(9):1882-1891. doi:10.7150/ijbs.31999 This issue Cite

Research Paper

An Autocrine IL-6/IGF-1R Loop Mediates EMT and Promotes Tumor Growth in Non-small Cell Lung Cancer

Xianan Zheng¹, Guohua Lu², Yinan Yao^2✉, Wei Gu^1✉

1. Department of Endocrinology, the Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China
2. Department of Respiratory Diseases, the First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China

Citation:

Zheng X, Lu G, Yao Y, Gu W. An Autocrine IL-6/IGF-1R Loop Mediates EMT and Promotes Tumor Growth in Non-small Cell Lung Cancer. Int J Biol Sci 2019; 15(9):1882-1891. doi:10.7150/ijbs.31999. https://www.ijbs.com/v15p1882.htm

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Abstract

Epithelial-to-mesenchymal transition (EMT) is a key process in EGFR-TKI resistance but the detailed mechanism is largely unknown. We aim to evaluate the role of interleukin-6 (IL-6) and insulin-like growth factor-1 receptor (IGR-1R) in EMT in non-small cell lung cancer (NSCLC). We used IL-6 to induce EMT in EGFR-TKI sensitive NSCLC cells. We found that both STAT3 and IGF-1R were activated. Interestingly activation of STAT3 and JAK1 was blocked by inhibiting IGF-1R, suggesting that IGF-1R might signal via JAK/STAT3. Activation of IGF-1R and AKT was inhibited by blocking STAT3, suggesting that STAT3 blockade might provide negative feedback signal to inhibiting IGF-1R. Reporter assay further confirmed that STAT3 activated gene transcription of IGF-1R. RT-PCR analyses showed that IL-6 induced the expression of IL-6 per se as well as IGF-1 and IGF-2. Expression of IL-6 and IGF-1R ligands was suppressed by inhibiting either STAT3 or IGF-1R. Meanwhile IL-6 induced gefitinib resistance and increased migration. We elucidated an autocrine loop of IL-6/IGF-1R/STAT3 in EMT-mediated resistance and tumor growth in NSCLC.

Keywords: IGF-1, STAT3, epithelial-to-mesenchymal, transition, IL-6, NSCLC

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APA

Zheng, X., Lu, G., Yao, Y., Gu, W. (2019). An Autocrine IL-6/IGF-1R Loop Mediates EMT and Promotes Tumor Growth in Non-small Cell Lung Cancer. International Journal of Biological Sciences, 15(9), 1882-1891. https://doi.org/10.7150/ijbs.31999.

ACS

Zheng, X.; Lu, G.; Yao, Y.; Gu, W. An Autocrine IL-6/IGF-1R Loop Mediates EMT and Promotes Tumor Growth in Non-small Cell Lung Cancer. Int. J. Biol. Sci. 2019, 15 (9), 1882-1891. DOI: 10.7150/ijbs.31999.

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CSE

Zheng X, Lu G, Yao Y, Gu W. 2019. An Autocrine IL-6/IGF-1R Loop Mediates EMT and Promotes Tumor Growth in Non-small Cell Lung Cancer. Int J Biol Sci. 15(9):1882-1891.

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