TSPAN12 Precedes Tumor Proliferation by Cell Cycle Control in Ovarian Cancer

Mol Cells. 2019 Jul 31;42(7):557-567. doi: 10.14348/molcells.2019.0015.

Abstract

TSPAN12, a member of the tetraspanin family, has been highly connected with the pathogenesis of cancer. Its biological function, however, especially in ovarian cancer (OC), has not been well elucidated. In this study, The Cancer Genome Atlas (TCGA) dataset analysis revealed that upregulation of TSPAN12 gene expression was significantly correlated with patient survival, suggesting that TSPAN12 might be a potential prognostic marker for OC. Further exploration showed that TSPAN12 overexpression accelerated proliferation and colony formation of OVCAR3 and SKOV3 OC cells. Knockdown of TSPAN12 expression in A2780 and SKOV3 cells decreased both proliferation and colony formation. Western blot analysis showed that several cyclins and cyclin-dependent kinases (CDK) (e.g., Cyclin A2, Cyclin D1, Cyclin E2, CDK2, and CDK4) were significantly involved in the regulation of cell cycle downstream of TSPAN12. Moreover, TSPAN12 accelerated mitotic progression by controlling cell cycle. Thus, our data demonstrated that TSPAN12 could be a novel molecular target for the treatment of OC.

Keywords: TSPAN12; cell cycle; ovarian cancer; proliferation.

MeSH terms

  • Animals
  • Cell Cycle Checkpoints*
  • Cell Line, Tumor
  • Cell Proliferation
  • Cyclin-Dependent Kinases / metabolism
  • Cyclins / metabolism
  • Female
  • Humans
  • Mice, Inbred BALB C
  • Mice, Nude
  • Ovarian Neoplasms / pathology*
  • Prognosis
  • Tetraspanins / metabolism*
  • Tumor Stem Cell Assay

Substances

  • Cyclins
  • TSPAN12 protein, human
  • Tetraspanins
  • Cyclin-Dependent Kinases