Histidine‐rich calcium binding protein promotes growth of hepatocellular carcinoma in vitro and in vivo. Issue 10 (13th August 2015)

• Record Type: Journal Article
• Authors: Liu, Jingmei; Han, Ping; Li, Mengke; Yan, Wei; Liu, Jiqiao; He, Jiayi; Gong, Jin; Wang, Yunwu; Tian, Dean
• Is Part Of: Cancer science. Volume 106:Issue 10(2015:Oct.)
• Page Start: 1288
• Page End: 1295
• Publication Date: 2015-08-13
• Subjects: Apoptosis -- endoplasmic reticulum stress -- hepatocellular carcinoma -- histidine‐rich calcium binding protein -- proliferation; Cancer -- Periodicals; Neoplasms -- Periodicals; Research -- Periodicals; Electronic journals; 616.994005
• DOI: 10.1111/cas.12743
• Languages: English
• ISSNs: 1347-9032

Abstract

Abstract : We have recently shown that the histidine‐rich calcium binding protein (HRC) promotes the invasion and metastasis of hepatocellular carcinoma (HCC). In the current study, we evaluated whether HRC may also affect the growth of HCC. We found that ectopic expression of HRC obviously enhanced proliferation and colony formation, while suppression of HRC exhibited inhibitory effects. Furthermore, we demonstrated that HRC promoted tumor growth in nude mice. These effects may result from the ability of HRC to upregulate cyclinD1 and cyclin‐dependent kinase 2 (CDK2) expressions and promote G1/S transition. Further study showed that MEK/ERK signaling pathway was involved in HRC‐induced cell proliferation. Interestingly, overexpression or depletion of HRC revealed its regulation on endoplasmic reticulum stress (ERS) and apoptosis, which was partially dependent on PERK/ATF4/CHOP signaling pathway. In addition, blocking ERS using 4‐phenylbutyric acid (4‐PBA) not only downregulated the expression of PERK, ATF4 and CHOP, but also significantly decreased apoptosis induced by HRC silence, whereas ERS inducer thapsigargin (TG) exerted the opposite effects. Our study thus demonstrates a role of HRC in promoting HCC growth, besides its role in inducing HCC metastasis, and highlights HRC as a promising intervention target for HCC. Abstract : HRC regulates proliferation, colony formation, cell cycle and apoptosis in vitro and promotes tumor growth of HCC in vivo .MEK/ERK pathway and ER stress are involved in the effect of HRC on HCC.