Related Experiment Video

Updated: Sep 2, 2025

Methods to Study Mrp4-containing Macromolecular Complexes in the Regulation of Fibroblast Migration
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PFKFB4 interacts with ICMT and activates RAS/AKT signaling-dependent cell migration in melanoma

Méghane Sittewelle1,2, Vincent Kappès1,2, Chenxi Zhou1,2

  • 1Université Paris-Saclay, Faculté des Sciences d'Orsay, CNRS UMR 3347, INSERM U1021, Orsay, France.

Life Science Alliance
|August 1, 2022
PubMed

Insights

Phosphofructokinase-FB4 (PFKFB4) has a novel role in melanoma cell migration, independent of its metabolic functions. It interacts with ICMT to enhance RAS-AKT signaling, promoting cancer cell movement.

Area of Science:

  • Oncology
  • Cell Biology
  • Biochemistry

Background:

  • Cell migration is crucial for development and cancer metastasis.
  • RAS-dependent signaling pathways, including PI3K/AKT, regulate cell migration.
  • PFKFB4 is a known regulator of glycolysis and the Warburg effect in cancer.

Purpose of the Study:

  • To investigate a novel function of PFKFB4 in melanoma cell migration.
  • To explore the link between PFKFB4, RAS signaling, and cell migration in human cancers.

Main Methods:

  • Investigated the interaction between PFKFB4 and ICMT (isoprenylcysteine carboxyl methyltransferase).
  • Assessed the effect of PFKFB4 on RAS localization and AKT signaling.
  • Evaluated the impact on melanoma cell migration.

Main Results:

  • PFKFB4 interacts with ICMT, a RAS posttranslational modifier.
  • PFKFB4 enhances the interaction between ICMT and RAS.
  • PFKFB4 promotes RAS plasma membrane localization, activates AKT signaling, and increases melanoma cell migration.
  • This function of PFKFB4 is independent of its role in glycolysis.

Conclusions:

  • PFKFB4 has a novel, glycolysis-independent role in promoting melanoma cell migration.
  • PFKFB4 links metabolic regulation to RAS-AKT signaling, impacting cancer cell motility.
  • This finding reveals a new therapeutic target for melanoma metastasis.

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