PT  - JOURNAL ARTICLE
AU  - Xiao, Qianyi
AU  - Qu, Kai
AU  - Wang, Chenji
AU  - Kong, Yahui
AU  - Liu, Chao
AU  - Jiang, Deke
AU  - Saiyin, Hexige
AU  - Jia, Fan
AU  - Ni, Canrong
AU  - Chen, Taoyang
AU  - Zhang, Yuanyuan
AU  - Zhang, Pingzhao
AU  - Qin, Wenxin
AU  - Sun, Qingwen
AU  - Wang, Hongyang
AU  - Yi, Qing
AU  - Liu, Jun
AU  - Huang, Haojie
AU  - Yu, Long
TI  - HDGF-related protein-3 is required for anchorage-independent survival and chemoresistance in hepatocellular carcinomas
AID  - 10.1136/gutjnl-2011-300781
DP  - 2013 Mar 01
TA  - Gut
PG  - 440--451
VI  - 62
IP  - 3
4099  - http://gut.bmj.com/content/62/3/440.short
4100  - http://gut.bmj.com/content/62/3/440.full
SO  - Gut2013 Mar 01; 62
AB  - Objective Hepatoma-derived growth factor (HDGF)-related proteins (HRPs) comprise a family of six members and are characterised by a conserved HATH domain. Among the family members, HDGF was the first to be identified as a mitogenic factor and shown to play an important role in hepatocellular carcinoma pathogenesis. The aim of the present study is to examine the relevance of HDGF-related protein-3 (HRP-3), another member of the HRP family in hepatocellular carcinoma (HCC). Design HRP-3 expression in HCC tissues was measured by quantitative reverse transcriptase PCR, western blot and immunohistochemistry analysis. The biological consequences of overexpression and knockdown of HRP-3 in HCC cell lines were studied in vitro and in vivo. Results Expression of HRP-3 mRNA and protein was shown to be highly upregulated in HCC tissues. While knockdown of HRP-3 by small interference RNAs failed to affect anchorage-dependent growth of HCC cells, it inhibited anchorage-independent growth of HCC cells in vitro and xenograft tumour growth in vivo. Further, knockdown of HRP-3 was shown to sensitise HCC cells to anoikis. Moreover, HRP-3 specifically activated the extracellular-signal-regulated kinase (ERK) pathway without affecting c-Jun N-terminal kinase (JNK), p38, AKT and signal transducer and activator of transcription 3 (STAT3). Importantly, inhibition of the ERK pathway diminished HRP-3-mediated protection of HCC cells from anoikis. Finally, knockdown of HRP-3 was shown to enhance apoptosis of HCC cells induced by multiple chemotherapeutic drugs. Conclusion These findings indicate that HRP-3 plays an essential role in HCC pathogenesis and suggest that it may serve as a novel prognostic marker and molecular target for development of drugs for treatment of HCC.