ING4 suppresses tumor angiogenesis and functions as a prognostic marker in human
colorectal cancer
#MMPMID27806345
Chen Y
; Huang Y
; Hou P
; Zhang Z
; Zhang Y
; Wang W
; Sun G
; Xu L
; Zhou J
; Bai J
; Zheng J
Oncotarget
2016[Nov]; 7
(48
): 79017-79031
PMID27806345
show ga
ING4, a potential tumor suppressor, is implicated in cell cycle arrest,
apoptosis, cell migration and angiogenesis. Here, we investigated the clinical
value of ING4 and its impact on angiogenesis in colorectal cancer (CRC). In this
study, we found that ING4 expression was significantly reduced in CRC tissues
versus paired normal colon tissues. Moreover, low ING4 expression was
significantly associated with increased lymph node metastasis, advanced TNM stage
and poor overall survival. Multivariate Cox regression analysis showed that ING4
expression was an independent favourable prognostic factor for CRC (hazard ratio
= 0.45, P = 0.001). In addition, we found that ING4 strongly inhibited CRC
angiogenesis by suppressing Sp1 expression and transcriptional activity through
ubiquitin degradation and down-regulating the expressions of Sp1 downstream
pro-angiogenic genes, MMP-2 and COX-2. Moreover, ING4 might inhibit
phosphorylation activity of cyclin/CDK2 complexes to trigger Sp1 degradation by
inducing p21 expression in despite of p53 status. Our findings imply that reduced
ING4 expression in CRC resulted in increased angiogenesis and contributed to CRC
metastasis and poor prognosis. Restoration of ING4 may be a novel strategy for
the treatment of metastatic CRC.
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