RT Journal Article
SR Electronic
T1 HDGF-related protein-3 is required for anchorage-independent survival and chemoresistance in hepatocellular carcinomas
JF Gut
JO Gut
FD BMJ Publishing Group Ltd and British Society of Gastroenterology
SP 440
OP 451
DO 10.1136/gutjnl-2011-300781
VO 62
IS 3
A1 Xiao, Qianyi
A1 Qu, Kai
A1 Wang, Chenji
A1 Kong, Yahui
A1 Liu, Chao
A1 Jiang, Deke
A1 Saiyin, Hexige
A1 Jia, Fan
A1 Ni, Canrong
A1 Chen, Taoyang
A1 Zhang, Yuanyuan
A1 Zhang, Pingzhao
A1 Qin, Wenxin
A1 Sun, Qingwen
A1 Wang, Hongyang
A1 Yi, Qing
A1 Liu, Jun
A1 Huang, Haojie
A1 Yu, Long
YR 2013
UL http://gut.bmj.com/content/62/3/440.abstract
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.