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TIMP1 Is a Prognostic Marker for the Progression and Metastasis of Colon Cancer Through FAK-PI3K/AKT and MAPK Pathway

TIMP1 Is a Prognostic Marker for the Progression and Metastasis of Colon Cancer Through FAK-PI3K/AKT and MAPK Pathway

Guohe Song, Shifeng Xu, Hong Zhang, Yupeng Wang, Chao Xiao, Tao Jiang, Leilei Wu, Tao Zhang, Xing Sun, Lin Zhong, Chongzhi Zhou, Zhaowen Wang, Zhihai Peng, Jian Chen, Xiaoliang Wang

J Exp Clin Cancer Res. 2016 Sep 20;35(1):148.

PMID: 27644693

Abstract:

Background:
Tissue inhibitor matrix metalloproteinase 1 (TIMP1) plays a vital role in carcinogenesis, yet its precise functional roles and regulation remain unclear. In this study, we aim to investigate its biological function and clinical significance in human colon cancer.
Methods:
We analyzed the expression of TIMP1 in both public database (Oncomine and TCGA) and 94 cases of primary colon cancer and matched normal colon tissue specimens. The underlying mechanisms of altered TIMP1 expression on cell tumorigenesis, proliferation, and metastasis were explored in vitro and in vivo.
Results:
TIMP1 was overexpressed in colon tumorous tissues and lymph node metastasis specimens than in normal tissues. The aberrant expression of TIMP1 was significantly associated with the regional lymph node metastasis (p = 0.033), distant metastasis (p = 0.039), vascular invasion (p = 0.024) and the American Joint Committee on Cancer (AJCC) stage (p = 0.026). Cox proportional hazards model showed that TIMP1 was an independent prognostic indicator of disease-free survival (HR = 2.603, 95 % CI: 1.115-6.077, p = 0.027) and overall survival (HR = 2.907, 95 % CI: 1.254-6.737, p = 0.013) for patients with colon cancer. Consistent with this, our findings highlight that suppression of TIMP1 expression decreased proliferation, and metastasis but increased apoptosis by inducing TIMP1 specific regulated FAK-PI3K/AKT and MAPK pathway.
Conclusion:
TIMP1 might play an important role in promoting tumorigenesis and metastasis of human colon cancer and function as a potential prognostic indicator for colon cancer.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR4241310	TIMP1 human			Price

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