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: UNIPROT:P10145 (
IL-8
)
23,849
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Centrosomal P4.1-associated protein
(
CPAP
) is overexpressed in hepatocellular carcinoma (HCC) and positively correlated with recurrence and vascular invasion. Here, we found that
CPAP
plays an important role in HCC malignancies. Functional characterization indicated that
CPAP
overexpression increases tumor growth, angiogenesis, and metastasis ex vivo and in vivo. In addition, overexpressed
CPAP
contributes to sorafenib resistance. Mechanical investigation showed that the expression level of
CPAP
is positively correlated with activated STAT3 in HCC.
CPAP
acts as a transcriptional coactivator of STAT3 by directly binding with STAT3. Interrupting the interaction between
CPAP
and STAT3 attenuates STAT3-mediated tumor growth and angiogenesis. Overexpression of
CPAP
upregulates several STAT3 target genes such as
IL-8
and CD44 that are involved in angiogenesis, and
CPAP
mRNA expression is positively correlated with the levels of both mRNAs in HCC. Knocked-down expression of
CPAP
impairs IL-6-mediated STAT3 activation, target gene expression, cell migration, and invasion abilities. IL-6/STAT3-mediated angiogenesis is significantly increased by
CPAP
overexpression and can be blocked by decreased expression of
IL-8
. Our findings not only shed light on the importance of
CPAP
in HCC malignancies, but also provide potential therapeutic strategies for inhibiting the angiogenesis pathway and treating metastatic HCC.
...
PMID:CPAP promotes angiogenesis and metastasis by enhancing STAT3 activity. 3151 51
