RIPOR2 promotes multinucleation of melanoma cells downstream of the RAS/ERK oncogenic pathway

Axelle Wilmerding1, Aurélie Richard2, Nicolas Macagno3,4

  • 1Aix-Marseille University, CNRS, IBDM, UMR 7288, Marseille, France.

Iscience
|May 8, 2026
PubMed

Insights

RAS/ERK pathway overactivation drives melanoma by upregulating RIPOR2, a gene promoting multinucleation. This finding offers a potential therapeutic target for melanoma treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Multinucleation in cancer is linked to aneuploidy and tumor aggressiveness.
  • Melanoma, characterized by melanocyte overproliferation, involves RAS/ERK pathway hyperactivation.

Purpose of the Study:

  • To investigate the role of RAS/ERK pathway targets in melanoma development.
  • To identify novel therapeutic targets for melanoma.

Main Methods:

  • Single-nucleus RNA sequencing in a chicken embryo model with RAS/ERK pathway overactivation.
  • Analysis of RIPOR2 expression and function in human melanoma cells and an animal model.

Main Results:

  • RIPOR2 was identified as a positive transcriptional target of the RAS/ERK pathway, conserved in human melanoma.
  • Ectopic RIPOR2 expression in human melanoma promotes multinucleation.
  • RIPOR2 functions as an atypical RHOA inhibitory protein.

Conclusions:

  • RIPOR2, upregulated by RAS/ERK signaling, contributes to melanoma pathogenesis by inducing multinucleation.
  • RIPOR2 represents a potential therapeutic target for melanoma.

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