Human tumor necrosis factor TNF-alpha-induced protein 8-like 2 suppresses hepatocellular carcinoma metastasis through inhibiting Rac1Reportar como inadecuado




Human tumor necrosis factor TNF-alpha-induced protein 8-like 2 suppresses hepatocellular carcinoma metastasis through inhibiting Rac1 - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Molecular Cancer

, 12:149

First Online: 26 November 2013Received: 27 August 2013Accepted: 21 November 2013DOI: 10.1186-1476-4598-12-149

Cite this article as: Cao, X., Zhang, L., Shi, Y. et al. Mol Cancer 2013 12: 149. doi:10.1186-1476-4598-12-149

Abstract

BackgroundTumor invasion and metastasis are the major reasons for leading death of patients with hepatocellular carcinoma HCC. Therefore, to identify molecules that can suppress invasion and metastasis of tumor will provide novel targets for HCC therapies. Tumor necrosis factor TNF-alpha-induced protein 8-like 2, TIPE2, is a novel immune negative molecule and an inhibitor of the oncogenic Ras in mice but its function in human is unclear. Our previous research has shown that TIPE2 is downregulated in human primary HCC compared with the paired adjacent non-tumor tissues.

ResultsIn present study, we provide evidence that TIPE2 inhibits effectively human hepatocellular carcinoma metastasis. The forced expression of TIPE2 in HCC-derived cell lines markedly inhibits tumor cell growth, migration and invasion in vitro and suppresses growth and metastasis of HCC in vivo. Clinical information from a cohort of 112 patients reveals that loss or reduced expression of TIPE2 in primary HCC tissues is significantly associated with tumor metastasis. Mechanically, TIPE2 inhibits the migration and invasion through targeting Rac1 and then reduces F-actin polymerization and expression of matrix metallopeptidase 9 MMP9 and urokinase plasminogen activator uPA.

ConclusionOur results indicate that human TIPE2 is endogenous inhibitor of Rac1 in HCC by which it attenuates invasion and metastasis of HCC. The data suggest that TIPE2 will be a new target for HCC therapy.

KeywordsTIPE2 HCC Invasion Metastasis Rac1 AbbreviationsHCCHepatocellular carcinoma

TIPE2Tumor necrosis factor TNF-alpha-induced protein 8-like 2

IHCImmunohistochemistry

RT-PCRReverse-transcriptase polymerase chain reaction

co-IPCo-immunoprecipitation

MMPMatrix metallopeptidase

uPAUrokinase plasminogen activator

AFPAlpha-fetoprotein.

Electronic supplementary materialThe online version of this article doi:10.1186-1476-4598-12-149 contains supplementary material, which is available to authorized users.

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Autor: Xuelei Cao - Li Zhang - Yongyu Shi - Yue Sun - Shen Dai - Chun Guo - Faliang Zhu - Qun wang - Jianing Wang - Xiaoyan Wan

Fuente: https://link.springer.com/



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