title: Cep70 overexpression stimulates pancreatic cancer by inducing centrosome abnormality and microtubule disorganization.
abstract: The centrosome is crucial for mitotic fidelity, and centrosome aberrations are associated with genomic instability and tumorigenesis. The centrosomal protein Cep70 has been reported to play a role in various cellular activities. However, whether this protein is involved in pathological processes remains unknown. In this study, we demonstrate that Cep70 is highly expressed in pancreatic cancer tissues. Cep70 expression correlates with clinicopathological parameters of pancreatic cancer, including histological grade, pathological tumor node metastasis stage, lymph node metastasis, and carbohydrate antigen 19-9 level. Depletion of Cep70 significantly suppresses pancreatic cancer cell proliferation and promotes apoptotic cell death, and exogenous expression of Cep70 can rescue the above effects. Cep70 also stimulates colony formation in soft agar and enhances tumor growth in mice. Our data further show that ectopic expression of Cep70 in pancreatic cancer cells results in the mislocalization of centrosomal proteins, including γ-tubulin and pericentrin, and the formation of intracellular aggregates. In addition, Cep70 overexpression leads to microtubule disorganization and the formation of multipolar spindles during mitosis. Our study thus unravels a critical role for Cep70 in pancreatic cancer and suggests Cep70 as a potential biomarker and therapeutic target for this deadly disease.
authors.affiliation: Institute of Biomedical Sciences, College of Life Sciences, Key Laboratory of Animal Resistance of Shandong Province, Key Laboratory of Molecular and Nano Probes of the Ministry of Education, Shandong Normal University, Jinan 250014, China.|State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071, China.
authors.forename: Songbo
authors.initials: S
authors.lastname: Xie
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Qin
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071, China.
authors.forename: Shiyu
authors.initials: S
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071, China.
authors.forename: Yijun
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071, China.
authors.forename: Xingjuan
authors.initials: X
authors.lastname: Shi
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071, China.
authors.forename: Dengwen
authors.initials: D
authors.lastname: Li
authors.affiliation: Institute of Biomedical Sciences, College of Life Sciences, Key Laboratory of Animal Resistance of Shandong Province, Key Laboratory of Molecular and Nano Probes of the Ministry of Education, Shandong Normal University, Jinan 250014, China.|State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Institute of Biomedical Sciences, College of Life Sciences, Key Laboratory of Animal Resistance of Shandong Province, Key Laboratory of Molecular and Nano Probes of the Ministry of Education, Shandong Normal University, Jinan 250014, China.
authors.forename: Min
authors.initials: M
authors.lastname: Liu
mesh_terms: D000818:Animals; D017209:Apoptosis; D018797:Cell Cycle Proteins / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018385:Centrosome / Q000378:metabolism*; D056915:DNA Copy Number Variations; D004195:Disease Models, Animal; D000066630:Ectopic Gene Expression; D015870:Gene Expression; D064593:Heterografts; D006801:Humans; D008297:Male; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D008870:Microtubules / Q000378:metabolism*; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D008941:Spindle Apparatus / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D008869:Microtubule-Associated Proteins; C574386:CEP70 protein, human