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: EC:3.4.24.35 (
matrix metalloproteinase 9
)
2,207
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The
nuclear receptor coactivator 5
(
NCOA5
) displays both coactivator and corepressor functions. Previous studies showed that alteration of
NCOA5
participates in carcinogenesis and progression. However, its roles in colorectal cancer (CRC) remain unknown. Herein, we demonstrated that expression of
NCOA5
in human CRC tissues was notably higher than that in adjacent tissues, which significantly correlated with clinicopathological features such as length of tumor, regional lymph node staging and cancer staging. Knockdown of
NCOA5
markedly suppressed proliferation, migration and invasion of SW620 high malignant CRC cells. Silencing of
NCOA5
also inhibited
in vivo
growth of SW620 CRC subcutaneously xenografted tumors in athymic BALB/c nude mice. Meanwhile, Overexpression of
NCOA5
facilitated these processes in SW480 low malignant CRC cells. Furthermore, knockdown of
NCOA5
induced cell cycle G1 phase arrest in SW620 cells, whereas overexpression of
NCOA5
promoted G1 to S phase transition in SW480 cells. Mechanistic studies revealed that
NCOA5
upregulated phospho-protein kinase B (p-PKB/AKT), Cyclin D1 and matrix metalloproteinase 9 (MMP9) as well as downregulated P27 in CRC cells. Notably, PI3K inhibitor LY294002 obviously attenuated the effects of
NCOA5
on p-AKT, Cyclin D1, P27 and
MMP9
. Moreover, LY294002 and knockdown of Cyclin D1 or
MMP9
remarkably blocked the tumor-promoting activity of
NCOA5
. Collectively,
NCOA5
promoted CRC cell proliferation, migration and invasion by upregulating Cyclin D1 and
MMP9
while downregulating P27 to a great extent via activating PI3K/AKT signaling pathway. These findings suggested that
NCOA5
exhibits an oncogenic effect in human CRC and represents a novel therapeutic target for CRC.
...
PMID:NCOA5 promotes proliferation, migration and invasion of colorectal cancer cells via activation of PI3K/AKT pathway. 2929 14
