title: Depletion of tissue factor suppresses hepatic metastasis and tumor growth in colorectal cancer via the downregulation of MMPs and the induction of autophagy and apoptosis.
abstract: Tissue factor (TF) is a significant risk factor for hepatic metastasis in patients with colorectal cancer (CRC). However, the mechanism by which TF promotes hepatic metastasis in CRC remains elusive. In this study, we first confirmed that TF expression was significantly correlated with lymph node metastasis, hepatic metastasis and TNM staging in clinical CRC samples, and found that TF expression in colon cancer cell lines was correlated with the invasion ability. Next, by employing TF-overexpressing LOVO cell line as a model we demonstrated that lentivirus mediated knockdown of TF suppressed the migration and invasion of LOVO cells in vitro, and hepatic metastasis of colorectal cancer in nude mice orthotopic model. Mechanistically, we found that TF knockdown decreases colony formation ability and induced autophagy and apoptosis of LOVO cells, and this was at least partly mediated by the activation of unfolded protein response/PERK signaling. In conclusion, our data provide new insight into hepatic metastasis of CRC. Agents targeting TF should be developed as adjuvant therapeutics for CRC metastasis.
authors: Department of General Surgery, Peking University First Hospital, Beijing, China.
authors: Maolin
authors: M
authors: Tian
authors: Yuanlian
authors: Y
authors: Wan
authors: Jianqiang
authors: J
authors: Tang
authors: Hui
authors: H
authors: Li
authors: Ge
authors: G
authors: Yu
authors: Jing
authors: J
authors: Zhu
authors: Shiqi
authors: S
authors: Ji
authors: Hui
authors: H
authors: Guo
authors: Nan
authors: N
authors: Zhang
authors: Weiren
authors: W
authors: Li
authors: Junwei
authors: J
authors: Gai
authors: Lei
authors: L
authors: Wang
authors: Lifang
authors: L
authors: Dai
authors: Die
authors: D
authors: Liu
authors: Liandi
authors: L
authors: Lei
authors: Shigong
authors: S
authors: Zhu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001343:Autophagy / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D019073:HT29 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000401:mortality / Q000556:secondary*; D008297:Male; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics; D015398:Signal Transduction; D016019:Survival Analysis; D013925:Thromboplastin / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D056811:Unfolded Protein Response / Q000235:genetics
chemical_list: D013925:Thromboplastin; D020782:Matrix Metalloproteinases