Mar 24, 2020

The glycolysis regulator PFKFB4 interacts with ICMTand activates RAS/AKT signaling-dependent cell migration in melanoma.

BioRxiv : the Preprint Server for Biology
M. SittewelleAnne H Monsoro-Burq

Abstract

Cell migration is a complex process, tightly regulated during embryonic development and abnormally activated during cancer metastasis. RAS-dependent signaling is a major nexus controlling essential cell parameters such as proliferation, survival and migration using downstream effectors among which the PI3K/AKT signaling. In melanoma, oncogenic mutations frequently enhance RAS, PI3K/AKT or MAP kinase signaling, in addition to other cancer hallmarks including the activation of metabolism regulators such as PFKFB4, a critical regulator of glycolysis and Warburg effect. Here, we explore a novel function of PFKFB4 in melanoma cell migration. We find that instead of acting as a kinase as recorded in glycolysis, PFKFB4 interacts with ICMT, a post-translational modifier of RAS. PFKFB4 promotes ICMT/RAS interaction, controls RAS addressing at the plasma membrane, activates AKT signaling and enhances cell migration. We thus evidence a novel glycolysis-independent function of PFKFB4 in human cancer cells. This unconventional activity links the metabolic regulator PFKFB4 to RAS-AKT signaling and impacts melanoma cell migration. Highlights- PFKFB4, a known regulator of glycolysis, displays an unconventional role in melanoma cell migration....Continue Reading

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Mentioned in this Paper

Genome-Wide Association Study
Protein Methylation
Genome
Genes
Environment
KIF1B
Hypogonadotropic Hypogonadism
Mutant Proteins
MAD2L1BP protein, human
Study of Epigenetics

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