CKAP2 Promotes Ovarian Cancer Proliferation and Tumorigenesis Through the FAK-ERK Pathway

DNA Cell Biol. 2017 Nov;36(11):983-990. doi: 10.1089/dna.2017.3876. Epub 2017 Sep 21.

Abstract

Upregulation of cytoskeleton-associated protein 2 (CKAP2) has been observed in ovarian cancer. This study aimed to determine the effects of overexpression of CKAP2 on cell proliferation and tumorigenesis and to explore the potential signal pathway in the oncogenic process. Expression of CKAP2 in tissue of ovarian cancer patients was detected. Human cancer cell line SKOV3 was overexpressed with CKAP2 and measured for cell growth and mobility. Moreover, CKAP2 effect was estimated using mouse tumor xenografts. mRNA expression levels of related genes were assessed. Expression levels of CKAP2 and p-ERK2 in SKOV3 cells were detected before and after treatment of focal adhesion kinase (FAK) inhibitor. mRNA and protein levels of CKAP2 were significantly elevated in human ovarian tumor tissues. Overexpression of CKAP2 in SKOV3 cells promoted cell proliferation and migration. Implantation of overexpressed SKOV3 cells showed significant tumorigenesis ability. mRNA expression levels of proliferating cell nuclear antigen (PCNA), matrix metalloproteinase 2 (MMP2), matrix metalloproteinase 9 (MMP9), and SNAI1 were elevated in overexpressed SKOV3 cells. Cells with CKAP2 overexpression also had significantly increased p-ERK2 level. Moreover, FAK inhibitor treatment significantly decreased CKAP2 expression levels as well as the phosphorylation level of ERK2 in SKOV3 cells. This study suggests that overexpression of CKAP2 enhanced proliferation and mobility of carcinoma cells through the FAK-ERK2 signaling pathway.

Keywords: CKAP2; FAK-ERK pathway; ovarian cancer; tumor-targeting; tumorigenesis.

MeSH terms

  • Animals
  • Apoptosis
  • Biomarkers, Tumor / metabolism
  • Carcinogenesis*
  • Case-Control Studies
  • Cell Proliferation*
  • Cytoskeletal Proteins / metabolism*
  • Female
  • Focal Adhesion Protein-Tyrosine Kinases / metabolism*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Mice
  • Mice, Nude
  • Mitogen-Activated Protein Kinase 1 / metabolism*
  • Mitogen-Activated Protein Kinase 3 / metabolism*
  • Neoplasm Invasiveness
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology*
  • Phosphorylation
  • Signal Transduction
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays

Substances

  • Biomarkers, Tumor
  • CKAP2 protein, human
  • Cytoskeletal Proteins
  • Focal Adhesion Protein-Tyrosine Kinases
  • MAPK1 protein, human
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3