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Downregulation of G3BPs inhibits the growth, migration and invasion of human lung carcinoma H1299 cells by suppressing the Src/FAK-associated signaling pathway

Cancer Gene Therapy volume 20, pages 622–629 (2013)Cite this article

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Abstract

G3BP is a RasGAP binding protein that is overexpressed in many human cancers. We previously reported that downregulation of G3BP suppressed cell growth and induced apoptosis in HCT116 cells. Here we report that both transient and stable knockdown of G3BP suppressed the growth, migration and invasion capability of human lung carcinoma H1299 cells. Moreover, downregulation of G3BP significantly inhibited the phosphorylation of Src, FAK and ERK, and the levels of NF-κB were also markedly decreased in H1299 cells. Knockdown of G3BP also decreased the expression of matrix metalloproteinase-2 (MMP-2), MMP-9 and plasminogen activator (uPA), and in vivo data demonstrated that downregulation of G3BP markedly inhibited the growth of H1299 tumor xenografts. Together, these data revealed that knockdown of G3BP inhibited the migration and invasion of human lung carcinoma cells through the inhibition of Src, FAK, ERK and NF-κB and decreased levels of MMP-2, MMP-9 and uPA.

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Acknowledgements

This project was supported by the grants from National 973 Program (No. 2009CB521807) and National Mega-project for Innovative Drugs (No. 2012ZX093 01-002), NSFC (No. 30772583 & 81273554), and IMB Fund.

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Authors and Affiliations

  1. Department of Oncology, Institute of Medicinal Biotechnology, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China

    H Zhang, S-h Zhang, H-w He, C-x Zhang, D-k Yu & R-g Shao

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Correspondence to R-g Shao.

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Zhang, H., Zhang, Sh., He, Hw. et al. Downregulation of G3BPs inhibits the growth, migration and invasion of human lung carcinoma H1299 cells by suppressing the Src/FAK-associated signaling pathway. Cancer Gene Ther 20, 622–629 (2013). https://doi.org/10.1038/cgt.2013.62

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