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Transforming Growth Factor β1 Promotes Migration and Invasion of Human Hepatocellular Carcinoma Cells Via Up-Regulation of Connective Tissue Growth Factor

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Abstract

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors with a poor patient survival. Expression of TGF-β1 is up-regulated in HCC and is thought to play a crucial role in the occurrence and development of HCC. However, the mechanism of TGF-β1-mediated facilitation of malignant growth and invasion remains unclear, although some previous studies highlighted a potential involvement of the connective tissue growth factor (CTGF). Here we demonstrate that the in vitro migration of the HCC cell line SMMC-7721 is increased in the presence of recombinant TGF-β1, and that this effect is reversed by the specific inhibitor SB431542. Furthermore, TGF-β1 treatment up-regulated the expression of its own mRNA as well as the expression of CTGF mRNA. The TGF-β1-stimulated migration of SMMC-7721 cells was diminished by siRNA silencing of CTGF. These in vitro observations were validated in a murine xenograft model. In particular, silencing of CTFG diminished the TGF-β1-induced tumorigenesis in experimental animals. In conclusion, TGF-β1 plays a critical role in HCC migration and invasion, and this effect is dependent on CTGF.

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Authors and Affiliations

  1. Department of Infectious Disease, Fuzhou General Hospital, Fuzhou, 350025, China

    Haizhou Liu, Shaoyang Wang, Weimin Ma & Youguang Lu

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  1. Haizhou Liu
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  2. Shaoyang Wang
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  4. Youguang Lu
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Correspondence to Haizhou Liu.

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Liu, H., Wang, S., Ma, W. et al. Transforming Growth Factor β1 Promotes Migration and Invasion of Human Hepatocellular Carcinoma Cells Via Up-Regulation of Connective Tissue Growth Factor. Cell Biochem Biophys 73, 775–781 (2015). https://doi.org/10.1007/s12013-015-0693-6

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  • DOI: https://doi.org/10.1007/s12013-015-0693-6

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