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TIMP1 is a prognostic marker for the progression and metastasis of colon cancer through FAK-PI3K/AKT and MAPK pathway
Department of General Surgery, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China.
Department of General Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, People’s Republic of China.
Örebro University, School of Medical Sciences.
Department of General Surgery, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China.
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2016 (English)In: Journal of Experimental & Clinical Cancer Research, ISSN 1756-9966, E-ISSN 1756-9966, Vol. 35, no 1, 148Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
London, United Kingdom: BioMed Central, 2016. Vol. 35, no 1, 148
Keyword [en]
TIMP1, Colon cancer, Prognosis, Tumorigenesis
National Category
Cancer and Oncology
Research subject
URN: urn:nbn:se:oru:diva-52526DOI: 10.1186/s13046-016-0427-7ISI: 000385276200001PubMedID: 27644693ScopusID: 2-s2.0-84988663611OAI: oai:DiVA.org:oru-52526DiVA: diva2:974322

Funding Agency:

National Nature Science Foundation of China 81472241  81270557

Available from: 2016-09-26 Created: 2016-09-26 Last updated: 2016-11-15Bibliographically approved

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