Discovery of Centrosomal Protein 70 as an Important Player in the Development and Progression of Breast Cancer

Am J Pathol. 2017 Mar;187(3):679-688. doi: 10.1016/j.ajpath.2016.11.005. Epub 2017 Jan 5.

Abstract

Centrosome abnormalities have been implicated in the development and progression of breast cancer. However, the molecular players involved in the above processes remain largely uncharacterized. Herein, we identify centrosomal protein 70 (Cep70) as an important factor that mediates breast cancer growth and metastasis. Cep70 is up-regulated in breast cancer tissues and cell lines, and its expression is closely correlated with several clinicopathologic variables associated with breast cancer progression. Mechanistic studies reveal that the up-regulation of Cep70 in breast cancer occurs at the mRNA level and is independent of gene amplification. Cep70 promotes breast cancer cell proliferation and colony formation in vitro and increases tumor growth in mice. In addition, Cep70 stimulates breast cancer cell migration and invasion in vitro. Bioluminescence imaging analysis further shows that Cep70 enhances breast cancer lung metastasis in mice. Together, these results demonstrate a critical role for Cep70 in the development and progression of breast cancer and have important implications in the diagnosis and therapy of this malignancy.

MeSH terms

  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology*
  • Carcinogenesis / metabolism*
  • Carcinogenesis / pathology*
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Disease Progression*
  • Female
  • Gene Dosage
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunohistochemistry
  • Luminescent Measurements
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism*
  • Neoplasm Invasiveness
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Tumor Stem Cell Assay

Substances

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