Journal Article

TIMP1 is a prognostic marker for the progression and metastasis of colon cancer through FAK-PI3K/AKT and MAPK pathway

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

2016

Overview

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.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V
• Subject: Adult / Aged / Aged, 80 and over / Apoptosis / Biological markers / Biomedical and Life Sciences / Biomedicine / Cancer Research / Care and treatment / Cell Line, Tumor / Cell Proliferation / Colon cancer / Colonic Neoplasms - genetics / Colonic Neoplasms - metabolism / Development and progression / Disease Progression / Disease-Free Survival / Female / Gene Expression Regulation, Neoplastic / HCT116 Cells / HT29 Cells / Humans / Immunology / Lymphatic Metastasis / Male / MAP Kinase Signaling System / Metastasis / Middle Aged / Oncology / Onkologi / Prognosis / Risk factors / Survival Analysis / TIMP1 / Tissue Inhibitor of Metalloproteinase-1 - genetics / Tissue Inhibitor of Metalloproteinase-1 - metabolism / Tumorigenesis / Up-Regulation