Protein tyrosine phosphatase 4A3 (PTP4A3/PRL-3) promotes the aggressiveness of human uveal melanoma through dephosphorylation of CRMP2

Scientific Reports
Laura DucielSimon Saule

Abstract

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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Citations

Jul 17, 2020·OncoTargets and Therapy·Yi Fan LiWen Bin Wei
Nov 12, 2020·International Journal of Molecular Sciences·Kalpana Mandal
Nov 9, 2021·Frontiers in Oncology·Thi Hai Yen NguyenDuc-Hau Le

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Methods Mentioned

BETA
co-immunoprecipitation
electrophoresis
immunoprecipitation
pull-down
pull down
pull downs
PCR
flow cytometry
optical tweezer
RNASeq

Software Mentioned

ImageJ64
StatView
Matlab
ImageJ
Metamorph
Genosplice

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