title: Cervical Cancer Growth Is Regulated by a c-ABL-PLK1 Signaling Axis.
abstract: The nonreceptor tyrosine kinase c-ABL controls cell growth but its contributions in solid tumors are not fully understood. Here we report that the Polo-like kinase PLK1, an essential mitotic kinase regulator, is an important downstream effector of c-ABL in regulating the growth of cervical cancer. c-ABL interacted with and phosphorylated PLK1. Phosphorylation of PLK1 by c-ABL inhibited PLK1 ubiquitination and degradation and enhanced its activity, leading to cell-cycle progression and tumor growth. Both c-ABL and PLK1 were overexpressed in cervical carcinoma. Notably, PLK1 tyrosine phosphorylation correlated with patient survival in cervical cancer. In a murine xenograft model of human cervical cancer, combination treatment with c-ABL and PLK1 inhibitors yielded additive effects on tumor growth inhibition. Our findings highlight the c-ABL-PLK1 axis as a novel prognostic marker and treatment target for human cervical cancers.Cancer Res; 77(5); 1142-54. ©2016 AACR.
authors.affiliation: State Key Laboratory of Proteomics, National Center for Protein Sciences, Beijing Institute of Radiation Medicine, Beijing, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Integrated Traditional Chinese Medicine and Western Medicine, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Chen
authors.affiliation: Beijing Institute of Biotechnology, Haidian District, Beijing, China.|Laboratory of Nuclear and Radiation Damage, The General Hospital of the PLA Rocket Force, Beijing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education, Tianjin Industrial Microbiology Key Lab, College of Biotechnology, Tianjin University of Science and Technology, Tianjin, China.
authors.forename: Changmin
authors.initials: C
authors.lastname: Peng
authors.affiliation: State Key Laboratory of Proteomics, National Center for Protein Sciences, Beijing Institute of Radiation Medicine, Beijing, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Proteomics, National Center for Protein Sciences, Beijing Institute of Radiation Medicine, Beijing, China.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Yang
authors.affiliation: Institute of Basic Medical Sciences, National Center of Biomedical Analysis, Beijing, China. peihuadong@hotmail.com caoc@nic.bmi.ac.cn tnli@ncba.ac.cn.
authors.forename: Teng
authors.initials: T
authors.lastname: Li
authors.affiliation: Beijing Institute of Biotechnology, Haidian District, Beijing, China. peihuadong@hotmail.com caoc@nic.bmi.ac.cn tnli@ncba.ac.cn.
authors.forename: Cheng
authors.initials: C
authors.lastname: Cao
authors.affiliation: State Key Laboratory of Proteomics, National Center for Protein Sciences, Beijing Institute of Radiation Medicine, Beijing, China. peihuadong@hotmail.com caoc@nic.bmi.ac.cn tnli@ncba.ac.cn.
authors.forename: Huadong
authors.initials: H
authors.lastname: Pei
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000378:metabolism*; D049109:Cell Proliferation / Q000502:physiology; D005260:Female; D057809:HEK293 Cells; D006367:HeLa Cells; D064593:Heterografts; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D016315:Proto-Oncogene Proteins c-abl / Q000378:metabolism*; D015398:Signal Transduction; D014162:Transfection; D002583:Uterine Cervical Neoplasms / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D000097869:Polo-Like Kinase 1
chemical_list: D018797:Cell Cycle Proteins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D016315:Proto-Oncogene Proteins c-abl; D000097869:Polo-Like Kinase 1