PMID- 26176291
OWN - NLM
STAT- MEDLINE
DCOM- 20160216
LR  - 20181113
IS  - 1349-7006 (Electronic)
IS  - 1347-9032 (Print)
IS  - 1347-9032 (Linking)
VI  - 106
IP  - 10
DP  - 2015 Oct
TI  - Histidine-rich calcium binding protein promotes growth of hepatocellular 
      carcinoma in vitro and in vivo.
PG  - 1288-95
LID - 10.1111/cas.12743 [doi]
AB  - 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.
CI  - (c) 2015 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on 
      behalf of Japanese Cancer Association.
FAU - Liu, Jingmei
AU  - Liu J
AD  - Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, China.
FAU - Han, Ping
AU  - Han P
AD  - Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, China.
FAU - Li, Mengke
AU  - Li M
AD  - Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, China.
FAU - Yan, Wei
AU  - Yan W
AD  - Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, China.
FAU - Liu, Jiqiao
AU  - Liu J
AD  - Department of Ultrasound, Tongji Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, China.
FAU - He, Jiayi
AU  - He J
AD  - Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, China.
FAU - Gong, Jin
AU  - Gong J
AD  - Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, China.
FAU - Wang, Yunwu
AU  - Wang Y
AD  - Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, China.
FAU - Tian, Dean
AU  - Tian D
AD  - Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150813
PL  - England
TA  - Cancer Sci
JT  - Cancer science
JID - 101168776
RN  - 0 (ATF4 protein, human)
RN  - 0 (Calcium-Binding Proteins)
RN  - 0 (DDIT3 protein, human)
RN  - 0 (Phenylbutyrates)
RN  - 0 (RNA, Small Interfering)
RN  - 139135-52-7 (HRC protein, human)
RN  - 145891-90-3 (Activating Transcription Factor 4)
RN  - 147336-12-7 (Transcription Factor CHOP)
RN  - 67526-95-8 (Thapsigargin)
RN  - 7WY7YBI87E (4-phenylbutyric acid)
RN  - EC 2.7.11.1 (EIF2AK3 protein, human)
RN  - EC 2.7.11.1 (eIF-2 Kinase)
RN  - EC 3.4.22.- (Caspase 3)
SB  - IM
MH  - Activating Transcription Factor 4/metabolism
MH  - Animals
MH  - Apoptosis/drug effects/*physiology
MH  - Calcium-Binding Proteins/biosynthesis/genetics/*metabolism
MH  - Carcinoma, Hepatocellular/*pathology
MH  - Caspase 3/metabolism
MH  - Cell Proliferation
MH  - Endoplasmic Reticulum Stress/drug effects/*physiology
MH  - G1 Phase Cell Cycle Checkpoints/genetics
MH  - Humans
MH  - Liver Neoplasms/*pathology
MH  - MAP Kinase Signaling System
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Nude
MH  - Neoplasm Transplantation
MH  - Phenylbutyrates/pharmacology
MH  - RNA Interference
MH  - RNA, Small Interfering
MH  - Thapsigargin/pharmacology
MH  - Transcription Factor CHOP/metabolism
MH  - Transplantation, Heterologous
MH  - eIF-2 Kinase/metabolism
PMC - PMC4638025
OTO - NOTNLM
OT  - Apoptosis
OT  - endoplasmic reticulum stress
OT  - hepatocellular carcinoma
OT  - histidine-rich calcium binding protein
OT  - proliferation
EDAT- 2015/07/16 06:00
MHDA- 2016/02/18 06:00
PMCR- 2015/10/01
CRDT- 2015/07/16 06:00
PHST- 2015/04/13 00:00 [received]
PHST- 2015/07/06 00:00 [revised]
PHST- 2015/07/09 00:00 [accepted]
PHST- 2015/07/16 06:00 [entrez]
PHST- 2015/07/16 06:00 [pubmed]
PHST- 2016/02/18 06:00 [medline]
PHST- 2015/10/01 00:00 [pmc-release]
AID - 10.1111/cas.12743 [doi]
PST - ppublish
SO  - Cancer Sci. 2015 Oct;106(10):1288-95. doi: 10.1111/cas.12743. Epub 2015 Aug 13.