Cep70 overexpression stimulates pancreatic cancer by inducing centrosome abnormality and microtubule disorganization

Sci Rep. 2016 Feb 19;6:21263. doi: 10.1038/srep21263.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Cell Cycle Proteins / genetics*
  • Cell Line, Tumor
  • Cell Proliferation
  • Centrosome / metabolism*
  • DNA Copy Number Variations
  • Disease Models, Animal
  • Ectopic Gene Expression
  • Gene Expression*
  • Heterografts
  • Humans
  • Male
  • Mice
  • Microtubule-Associated Proteins / genetics*
  • Microtubules / metabolism*
  • Neoplasm Grading
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Pancreatic Neoplasms / genetics*
  • Pancreatic Neoplasms / metabolism*
  • Pancreatic Neoplasms / pathology
  • Spindle Apparatus / metabolism

Substances

  • Cell Cycle Proteins
  • Cep70 protein, human
  • Microtubule-Associated Proteins