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Expression of the PTP4A3 gene, encoding a phosphatase, is predictive of poor patient survival. PTP4A3 expression in UM cells increases their migration <jats:italic>in vitro<\/jats:italic> and invasiveness <jats:italic>in vivo<\/jats:italic>. 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 <jats:italic>in vitro<\/jats:italic> and invasiveness <jats:italic>in vivo<\/jats:italic>. 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.<\/jats:p>","DOI":"10.1038\/s41598-019-39643-y","type":"journal-article","created":{"date-parts":[[2019,2,28]],"date-time":"2019-02-28T11:05:03Z","timestamp":1551351903000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Protein tyrosine phosphatase 4A3 (PTP4A3\/PRL-3) promotes the aggressiveness of human uveal melanoma through dephosphorylation of CRMP2"],"prefix":"10.1038","volume":"9","author":[{"given":"Laura","family":"Duciel","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oc\u00e9ane","family":"Anezo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kalpana","family":"Mandal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3022-2283","authenticated-orcid":false,"given":"C\u00e9cile","family":"Laurent","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Planque","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fr\u00e9d\u00e9ric M.","family":"Coquelle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Gentien","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8670-3940","authenticated-orcid":false,"given":"Jean-Baptiste","family":"Manneville","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Saule","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,2,28]]},"reference":[{"key":"39643_CR1","doi-asserted-by":"publisher","first-page":"670","DOI":"10.1001\/archopht.119.5.670","volume":"119","author":"Collaborative Ocular Melanoma Study Group","year":"2001","unstructured":"Collaborative Ocular Melanoma Study Group. 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