Kisspeptin Promotes Glioblastoma Cell Invasiveness Via the Gq-PLC-PKC Pathway

Anticancer Res. 2020 Jan;40(1):213-220. doi: 10.21873/anticanres.13942.

Abstract

Background/aim: Kisspeptin produced from the KISS1 gene is secreted from the living cells, binds to endogenous receptor KISS1R (also called G protein-coupled receptor 54, GPR54), and has various functions in normal physiological conditions. Although an anti-metastatic role of kisspeptin in cancer is well known in several cancer types, its role in brain tumors is not yet understood. Herein, we investigated a the role of kisspeptin in glioblastoma cells.

Materials and methods: Glioblastoma cells were treated with kisspeptin and subjected to proliferation, migration, and invasion assays. KISS1R dependency was tested by KISS1R silencing with KISS1R siRNAs.

Results: Kisspeptin inhibited migratory and invasive abilities of U87-MG, U-251-MG and U373-MG glioblastoma cells with no effect on cell viability. KISS1R gene silencing with KISS1R siRNAs blocked kisspeptin-induced glioblastoma cell invasiveness. Moreover, chemical inhibitors against Gq, PLC or PKC blocked kisspeptin-induced glioblastoma cell invasiveness.

Conclusion: Kisspeptin induces glioblastoma cell invasiveness via the KISS1R-Gq-PLC-PKC signaling pathway.

Keywords: Glioblastoma; KISS1; KISS1R; brain tumor; kisspeptin.

MeSH terms

  • Cell Line, Tumor
  • Enzyme Activation
  • GTP-Binding Protein alpha Subunits, Gq-G11 / metabolism*
  • Glioblastoma / metabolism*
  • Glioblastoma / pathology*
  • Humans
  • Kisspeptins / metabolism*
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Protein Kinase C / metabolism*
  • Signal Transduction*
  • Type C Phospholipases / metabolism*

Substances

  • Kisspeptins
  • Protein Kinase C
  • Type C Phospholipases
  • GTP-Binding Protein alpha Subunits, Gq-G11