Coupling function of cyclin-dependent kinase 2 and Septin2 in the promotion of hepatocellular carcinoma

Cancer Sci. 2019 Feb;110(2):540-549. doi: 10.1111/cas.13882. Epub 2018 Dec 26.

Abstract

Hepatocellular carcinoma (HCC) is a common and aggressive malignant tumor with a poorly defined molecular mechanism. Cyclin-dependent kinase 2 (CDK2) and Septin2 (SEPT2) are 2 known oncogenic molecules but the mechanism of functional interactions remains unclear. Here, we interestingly found that CDK2 and SEPT2 show very similar dynamic expression during the cell cycle. Both CDK2 and SEPT2 show the highest protein levels in the G2/M phase, resulting in CDK2 interacting with SEPT2 and stabilizing SEPT2 in HCC. In a panel of 8 pairs of fresh HCC tissues and corresponding adjacent tissues, both western blot and immunohistochemistry (IHC) assays demonstrate that CDK2 expression is highly correlated with SEPT2. HCC with high expression of both CDK2 and SEPT2 are more likely to relapse. This observation is further demonstrated by a large panel of 100 HCC patients. In this large panel, high expression of both CDK2 and SEPT2 significantly correlates with tumor differentiation and microvascular invasion, which is an independent prognostic factor in HCC patients. In summary, our results reveal a cooperative function between CDK2 and SEPT2. HCC with high expression of CDK2 and SEPT2 might be more aggressive and respond poorly to current therapy.

Keywords: CDK2; SEPT2; cell cycle; hepatocellular carcinoma; interaction.

MeSH terms

  • Animals
  • Carcinoma, Hepatocellular / metabolism*
  • Carcinoma, Hepatocellular / pathology*
  • Cell Line, Tumor
  • Cyclin-Dependent Kinase 2 / metabolism
  • Female
  • Humans
  • Immunohistochemistry / methods
  • Liver Neoplasms / metabolism*
  • Liver Neoplasms / pathology*
  • Male
  • Mice
  • Mice, Nude
  • Middle Aged
  • Neoplasm Recurrence, Local / metabolism
  • Neoplasm Recurrence, Local / pathology
  • Septins / metabolism*

Substances

  • Cyclin-Dependent Kinase 2
  • SEPTIN2 protein, human
  • Septins