title: TIMP1 is a prognostic marker for the progression and metastasis of colon cancer through FAK-PI3K/AKT and MAPK pathway.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of General Surgery, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200080, People's Republic of China.
authors.forename: Guohe
authors.initials: G
authors.lastname: Song
authors.affiliation: Department of General Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, 250021, People's Republic of China.
authors.forename: Shifeng
authors.initials: S
authors.lastname: Xu
authors.affiliation: School of Medicine, Örebro University, Örebro, SE 70182, Sweden.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200080, People's Republic of China.
authors.forename: Yupeng
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of General Surgery, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200080, People's Republic of China.
authors.forename: Chao
authors.initials: C
authors.lastname: Xiao
authors.affiliation: Department of General Surgery, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200080, People's Republic of China.
authors.forename: Tao
authors.initials: T
authors.lastname: Jiang
authors.affiliation: School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, 200031, People's Republic of China.
authors.forename: Leilei
authors.initials: L
authors.lastname: Wu
authors.affiliation: Department of General Surgery, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200080, People's Republic of China.
authors.forename: Tao
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200080, People's Republic of China.
authors.forename: Xing
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of General Surgery, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200080, People's Republic of China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhong
authors.affiliation: Department of General Surgery, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200080, People's Republic of China.
authors.forename: Chongzhi
authors.initials: C
authors.lastname: Zhou
authors.affiliation: Department of General Surgery, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200080, People's Republic of China.
authors.forename: Zhaowen
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of General Surgery, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200080, People's Republic of China.
authors.forename: Zhihai
authors.initials: Z
authors.lastname: Peng
authors.affiliation: Department of General Surgery, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200080, People's Republic of China. yufuchenjian@163.com.
authors.forename: Jian
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of General Surgery, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200080, People's Republic of China. xiaoliangwang1975@hotmail.com.
authors.forename: Xiaoliang
authors.initials: X
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism*; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D008207:Lymphatic Metastasis; D020935:MAP Kinase Signaling System; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016019:Survival Analysis; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics* / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: C560822:TIMP1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1
keywords: Colon cancer; Prognosis; TIMP1; Tumorigenesis