title: Cdk3-promoted epithelial-mesenchymal transition through activating AP-1 is involved in colorectal cancer metastasis.
abstract: Cyclin dependent kinase-3 (Cdk3) is a positive regulator of the G1 mammalian cell cycle phase. Cdk3 is involved in cancer progression, but very little is known about its mechanism in cancer development and progression. Herein, we found that Cdk3 increased colorectal cancer metastasis through promoting epithelial-mesenchymal transition (EMT) shift. Cdk3 was found to highly express in metastatic cancer and induce cell motility and invasion. Cdk3 was shown to phosphorylate c-Jun at Ser 63 and Ser 73 in vitro and ex vivo. Cdk3-phosphorylated c-Jun at Ser 63 and Ser 73 resulted in an increased AP-1 activity. Ectopic expression of Cdk3 promoted colorectal cancer from epithelial to mesenchymal transition conjugating AP-1 activation, while AP-1 inhibition dramatically decreased Cdk3-increased EMT shift. These results showed that the Cdk3/c-Jun signaling axis mediating epithelial-mesenchymal transition plays an important role in colorectal cancer metastasis.
authors.affiliation: Clinical Laboratory and Medical Research Center, Zhuhai Hospital of Jinan University, Zhuhai People's Hospital, Zhuhai, P.R. China.
authors.forename: Jinping
authors.initials: J
authors.lastname: Lu
authors.affiliation: Clinical Laboratory and Medical Research Center, Zhuhai Hospital of Jinan University, Zhuhai People's Hospital, Zhuhai, P.R. China.
authors.forename: Zhen Lin
authors.initials: ZL
authors.lastname: Zhang
authors.affiliation: Clinical Laboratory, Xiangya Hospital of Central South University, Changsha, P.R. China.
authors.forename: Damao
authors.initials: D
authors.lastname: Huang
authors.affiliation: Institution of Pathogenic Biology, Medical College, University of South China, Hengyang, P.R. China.
authors.forename: Na
authors.initials: N
authors.lastname: Tang
authors.affiliation: Clinical Laboratory and Medical Research Center, Zhuhai Hospital of Jinan University, Zhuhai People's Hospital, Zhuhai, P.R. China.
authors.forename: Yuejin
authors.initials: Y
authors.lastname: Li
authors.affiliation: Clinical Laboratory and Medical Research Center, Zhuhai Hospital of Jinan University, Zhuhai People's Hospital, Zhuhai, P.R. China.
authors.forename: Zhengke
authors.initials: Z
authors.lastname: Peng
authors.affiliation: Institution of Pathogenic Biology, Medical College, University of South China, Hengyang, P.R. China.
authors.forename: Chengrong
authors.initials: C
authors.lastname: Lu
authors.affiliation: Institution of Pathogenic Biology, Medical College, University of South China, Hengyang, P.R. China.
authors.forename: Zigang
authors.initials: Z
authors.lastname: Dong
authors.affiliation: Clinical Laboratory and Medical Research Center, Zhuhai Hospital of Jinan University, Zhuhai People's Hospital, Zhuhai, P.R. China.|Clinical Laboratory, Xiangya Hospital of Central South University, Changsha, P.R. China.
authors.forename: Faqing
authors.initials: F
authors.lastname: Tang
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D016022:Case-Control Studies; D002465:Cell Movement; D049109:Cell Proliferation; D003106:Colon / Q000378:metabolism / Q000473:pathology; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000556:secondary*; D056849:Cyclin-Dependent Kinase 3 / Q000378:metabolism*; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D007124:Immunoenzyme Techniques; D047468:Immunoprecipitation; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010766:Phosphorylation; D011379:Prognosis; D015398:Signal Transduction; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D018808:Transcription Factor AP-1; C098776:CDK3 protein, human; D056849:Cyclin-Dependent Kinase 3
keywords: AP-1; Cdk3; colorectal cancer; epithelial-mesenchymal transition; metastasis