Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0019204 (
hepatocellular carcinoma
)
71,386
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Recent studies have shown that the expression levels of glucose-regulated protein 78 (GRP78) and
homeobox B9
(
HOXB9
) are both upregulated in
hepatocellular carcinoma
(
HCC
) and are closely related to
HCC
invasion and metastasis. However, whether there is a regulatory relationship between GRP78 and
HOXB9
is unclear. In this study, we examined the expression of GRP78 and
HOXB9
in
HCC
tissues and adjacent nontumor tissues. Correlation analysis indicated that GRP78 and
HOXB9
expression were positively correlated. High levels of GRP78 and
HOXB9
expression are closely related to worse clinicopathological features. Knockdown of GRP78 in
HCC
cells decreased the mRNA and protein expression of
HOXB9
, but increase
HOXB9
expression reversed the decrease in invasion and metastasis induced by knocking down GRP78. Further experiments showed that GRP78 regulates
HOXB9
through the Wnt signaling pathway by chaperoning low-density lipoprotein receptor-related protein 6 (LRP6). Importantly, we found that GPR78 promoted maturation of LRP6, while knockdown of GRP78 led to LRP6 misfolding and endoplasmic reticulum-associated degradation (ERAD). Consequently, the levels of mature LRP6 were reduced, and Wnt/
HOXB9
signaling was inhibited. Our data suggest that the GRP78-LRP6-
HOXB9
axis regulates the invasion and metastasis of
HCC
and may represent a potential therapeutic target for the treatment of
HCC
.
...
PMID:GRP78 activates the Wnt/HOXB9 pathway to promote invasion and metastasis of hepatocellular carcinoma by chaperoning LRP6. 3131 Jul 47
