RGS2 Suppresses Melanoma Growth via Inhibiting MAPK and AKT Signaling Pathways

Anticancer Res. 2021 Dec;41(12):6135-6145. doi: 10.21873/anticanres.15433.

Abstract

Background/aim: This study aimed to explore RGS2 as a regulator of melanoma cell growth.

Materials and methods: Effect of RGS2 over-expression was analyzed in three melanoma cell lines, and Rgs2 knockdown was performed in zebrafish.

Results: RGS2 was differentially expressed among the cell lines. In B16F10 cells, RGS2 over-expression inhibited MAPK and AKT activation, and prevented cell growth. A similar outcome was observed in A375 cells, but the MAPK signals were not suppressed. In A2058 cells, RGS2 repressed AKT activation, but without affecting cell growth. Moreover, MAPK and AKT constitutive activation abolished the RGS2 inhibitory effect on B16F10 cell growth. Rgs2 knockdown caused ectopic melanocyte differentiation, and promoted MAPK and AKT activation in zebrafish embryos.

Conclusion: RGS2 prevents melanoma cell growth by inhibiting MAPK and AKT, but this effect depends on the overall cell genetic landscape. Further studies are warranted to investigate the anticancer therapeutic potential of RGS2 for melanoma.

Keywords: Rgs2/RGS2; melanocyte; melanoma; zebrafish.

MeSH terms

  • Animals
  • Helix-Loop-Helix Motifs / physiology*
  • Humans
  • Melanoma / drug therapy*
  • Melanoma / physiopathology
  • Mitogen-Activated Protein Kinase Kinases / metabolism*
  • Proto-Oncogene Proteins c-akt / metabolism*
  • RGS Proteins / pharmacology
  • RGS Proteins / therapeutic use*
  • Signal Transduction
  • Zebrafish

Substances

  • RGS Proteins
  • RGS2 protein, human
  • Proto-Oncogene Proteins c-akt
  • Mitogen-Activated Protein Kinase Kinases