Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
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Drug
Enzyme
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Query: UMLS:C0019204 (
hepatocellular carcinoma
)
71,386
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
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.
...
PMID:The histidine-rich calcium binding protein (HRC) promotes tumor metastasis in hepatocellular carcinoma and is upregulated by SATB1. 2576 22
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
.
...
PMID:Histidine-rich calcium binding protein promotes growth of hepatocellular carcinoma in vitro and in vivo. 2617 91
