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Fluorescence-based Monitoring of PAD4 Activity via a Pro-fluorescence Substrate Analog
Published on: November 5, 2014
ING4 suppresses tumor angiogenesis and functions as a prognostic marker in human colorectal cancer
Yansu Chen1,2, Yefei Huang1,2, Pingfu Hou1,3
1Jiangsu Key Laboratory of Biological Cancer Therapy, Xuzhou Medical University, Xuzhou 221002, Jiangsu Province, China.
Abstract:
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.
Insights
Reduced ING4 expression in colorectal cancer (CRC) correlates with increased metastasis and poor prognosis. Restoring ING4 may offer a new treatment strategy for metastatic CRC by inhibiting angiogenesis.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- ING4 is a potential tumor suppressor involved in cell cycle arrest, apoptosis, cell migration, and angiogenesis.
- Understanding ING4's role in colorectal cancer (CRC) is crucial for developing new therapeutic strategies.
Purpose of the Study:
- To investigate the clinical significance of ING4 expression in colorectal cancer (CRC).
- To determine the impact of ING4 on angiogenesis in CRC.
- To explore the molecular mechanisms by which ING4 affects CRC progression.
Main Methods:
- Quantitative analysis of ING4 expression in CRC tissues and paired normal colon tissues.
- Correlation analysis between ING4 expression levels and clinicopathological features (lymph node metastasis, TNM stage, overall survival).
- Investigation of ING4's effect on angiogenesis by examining Sp1, MMP-2, and COX-2 expression, and its influence on cyclin/CDK2 complexes and p21 expression.
Main Results:
- ING4 expression was significantly lower in CRC tissues compared to normal tissues.
- Low ING4 expression was associated with increased lymph node metastasis, advanced TNM stage, and poorer overall survival in CRC patients.
- ING4 inhibited CRC angiogenesis by suppressing Sp1 expression and its downstream genes (MMP-2, COX-2) possibly via p21 induction and Sp1 degradation, independent of p53 status.
Conclusions:
- Reduced ING4 expression in CRC promotes angiogenesis, contributing to metastasis and poor prognosis.
- ING4 serves as an independent favorable prognostic factor for CRC.
- Restoration of ING4 expression could be a potential therapeutic strategy for metastatic CRC.
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