Downregulation of CDK-8 inhibits colon cancer hepatic metastasis by regulating Wnt/β-catenin pathway.
Liver metastasis is a major cause of mortality from colon cancer. To investigate the role of cyclin-dependent kinase 8 (CDK8) in the progression of colon cancer hepatic metastasis. In this present study, human colon cancer HCT116 or HCT116-LUC-GFP cells were transfected with Lentiviral vector-mediated knockdown of CDK-8. After transfection, metastasis and invasion potential of colon cancer cell was investigated by wound healing and transwell invasion assays, respectively. A mice model of colon cancer liver metastases was established and observed with bioluminescence imaging. The protein expression of CDK-8, β-catenin, E2F1, MMP-7 and E-cadherin in liver tissues were detected by Western Blot. Our results revealed that lentiviral vector-mediated knockdown of CDK-8 inhibited metastasis and invasion of colon cancer cells in vitro and in vivo, respectively. Protein expression of CDK-8, β-catenin, MMP-7 and E-cadherin were inhibited, but protein expression of E2F1 was enhanced. In sum, our data provided compelling evidence that CDK-8 played a significant role in colon cancer hepatic metastasis by regulating the Wnt/β-catenin signal pathway and might sever as a potential therapeutic target for colon cancer patients.
Department of General Surgery, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou 510180, People's Republic of China.
Wen-Song
WS
Cai
Department of General Surgery, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou 510180, People's Republic of China.
Fei
F
Shen
Department of General Surgery, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou 510180, People's Republic of China.
Zhe
Z
Feng
Department of General Surgery, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou 510180, People's Republic of China.
Ji-Wei
JW
Chen
Experimental Medical Research Center, Guangzhou Medical University, Guangzhou 510182, People's Republic of China.
Qi-Cai
QC
Liu
Experimental Medical Research Center, Guangzhou Medical University, Guangzhou 510182, People's Republic of China.
Er-Mao
EM
Li
Department of General Surgery, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou 510180, People's Republic of China. Electronic address: xubo_cancer@163.com.
Bo
B
Xu
Department of General Surgery, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou 510180, People's Republic of China. Electronic address: aabb97@163.com.
Jie
J
Cao
D000818:Animals; D015153:Blotting, Western; D003110:Colonic Neoplasms / Q000235:genetics / Q000473:pathology*; D056850:Cyclin-Dependent Kinase 8 / Q000235:genetics*; D018450:Disease Progression; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D045325:HCT116 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000473:pathology* / Q000556:secondary; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness / Q000235:genetics; D014162:Transfection; D060449:Wnt Signaling Pathway / Q000235:genetics*; D014945:Wound Healing / Q000235:genetics
D056850:Cyclin-Dependent Kinase 8
Bioluminescence imaging; CDK-8; Colon cancer; Hepatic metastasis