The histidine-rich calcium binding protein (HRC) promotes tumor metastasis in hepatocellular carcinoma and is upregulated by SATB1

Oncotarget
Jingmei LiuDean Tian

Abstract

The histidine-rich calcium binding protein (HRC) is a regulator of Ca2+-homeostasis. Herein, we found that HRC was frequently upregulated in human hepatocellular carcinoma (HCC) tissues, and its expression was correlated with tumor size and metastasis. Moreover, HRC expression was positively related to the metastatic potential of HCC cell lines. Knockdown of HRC suppressed cell invasion and migration in vitro, whereas ectopic expression of HRC resulted in increased cell invasion and migration in vitro and intrahepatic and lung metastasis in vivo. Interestingly, the pro-invasion and pro-migration effects of HRC were associated with focal adhesion turnover, which was a consequence of FAK phosphorylation. Further experiments showed that HRC induced phospho-FAK, focal adhesion turnover and cell migration through Ca2+/CaM singaling. We found that HRC increased [Ca2+]i by inhibiting the expression of SERCA2. In addition, upregulation of HRC in HCC was attributed to SATB1, which is known to promote HCC metastasis. Ectopic expression of SATB1 enhanced HRC gene transcription by activating AP-1 in mainly a JNK-dependent manner. Our findings highlight HRC as a potential therapeutic target for HCC treatment.

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Citations

Sep 10, 2020·Molecular Biology Reports·Wala Ben Kridis-RejebRaja Mokdad-Gargouri
Oct 21, 2017·Oncotarget·Ying-Chen XuJi-Xiang Wu
Nov 21, 2018·Cell Death Discovery·Jingmei LiuDean Tian
Aug 25, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Jiacheng WuXuewen Zhang

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Methods Mentioned

BETA
xenograft
flow cytometry
co-immunoprecipitation
electrophoretic
immunoprecipitation
ChIP
PCR
Assay
X-ray

Software Mentioned

TFRESEARCH

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