Scientific Reports · 2019 · 21 citations · 45 references
Life SciencesCell BiologyOncologyCell SignalingMetastasisSignal TransductionCancer Cell SignalingCell MigrationMelanocytic TumorsProtein Phosphatase SignalingReceptor Tyrosine Kinase SignalingUveal MelanomaActin Network MechanicsAnterior Uveal MelanomaMelanoma ProgressionMetastatic Uveal MelanomaProtein Phosphatase ComplexesProtein Tyrosine Phosphatase InhibitorsUveal Melanoma MetastasisUveal Metastases
Uveal melanoma (UM) is an aggressive tumor in which approximately 50% of patients develop metastasis. Expression of the PTP4A3 gene, encoding a phosphatase, is predictive of poor patient survival. PTP4A3 expression in UM cells increases their migration in vitro and invasiveness in vivo. Here, we show that CRMP2 is mostly dephosphorylated on T514 in PTP4A3 expressing cells. We also demonstrate that inhibition of CRMP2 expression in UM cells expressing PTP4A3 increases their migration in vitro and invasiveness in vivo. This phenotype is accompanied by modifications of the actin microfilament network, with shortened filaments, whereas cells with a inactive mutant of the phosphatase do not show the same behavior. In addition, we showed that the cell cytoplasm becomes stiffer when CRMP2 is downregulated or PTP4A3 is expressed. Our results suggest that PTP4A3 acts upstream of CRMP2 in UM cells to enhance their migration and invasiveness and that a low level of CRMP2 in tumors is predictive of poor patient survival.
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Integrative Analysis Identifies Four Molecular and Clinical Subsets in Uveal Melanoma
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GSK-3β Regulates Phosphorylation of CRMP-2 and Neuronal Polarity
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CRMP-2 binds to tubulin heterodimers to promote microtubule assembly
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