title: LMW-PTP is a positive regulator of tumor onset and growth.
abstract: Low molecular weight protein tyrosine phosphatases (LMW-PTPs) are an enzyme family that plays a key role in cell proliferation control by dephosphorylating/inactivating both tyrosine kinase receptors (such as PDGF, insulin, and ephrin receptors) and docking proteins (such, as beta-catenin) endowed with both adhesion and transcriptional activity. Besides being a frequent event in human tumors, overexpression of LMW-PTP has been recently demonstrated to be sufficient to induce neoplastic transformation. We recently demonstrated that overexpression of LMW-PTP strongly potentiates the stability of cell-cell contacts at the adherens junction level, which powerfully suggests that LMW-PTP may also contribute to cancer invasivity. Focusing on mechanisms by which LMW-PTP is involved in cancer onset and progression, the emerging picture is that LMW-PTP strongly increases fibronectin-mediated cell adhesion and mobility but, paradoxically, decreases cell proliferation. Nevertheless, LMW-PTP-transfected NIH3T3 fibroblasts engrafted in nude mice induce the onset of larger fibrosarcomas, which are endowed with higher proliferation activity as compared to mock-transfected controls. Quite opposite effects have been obtained with engrafted fibroblasts transfected with a dominant-negative form of LMW-PTP. Notably, in sarcoma extracts, LMW-PTP overexpression greatly influences the ephrin A2 (EphA2) but not PDGF receptor or beta-catenin tyrosine phosphorylation. The high association of dephosphorylated EphA2 overexpression with most human cancers and our observation that cell growth stimulation by LMW-PTP overexpression is restricted to the in vivo model, strongly suggest that LMW-PTP oncogenic potential is mediated by its EphA2 tyrosine dephosphorylating activity.
authors.affiliation: Department of Biochemical Sciences of the University of Florence, viale Morgagni 50, 50134 Firenze, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Chiarugi
authors.forename: Maria Letizia
authors.initials: ML
authors.lastname: Taddei
authors.forename: Nicola
authors.initials: N
authors.lastname: Schiavone
authors.forename: Laura
authors.initials: L
authors.lastname: Papucci
authors.forename: Elisa
authors.initials: E
authors.lastname: Giannoni
authors.forename: Tania
authors.initials: T
authors.lastname: Fiaschi
authors.forename: Sergio
authors.initials: S
authors.lastname: Capaccioli
authors.forename: Giovanni
authors.initials: G
authors.lastname: Raugei
authors.forename: Giampietro
authors.initials: G
authors.lastname: Ramponi
mesh_terms: D000818:Animals; D007527:Isoenzymes / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D041681:NIH 3T3 Cells; D009369:Neoplasms / Q000201:enzymology* / Q000378:metabolism; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins; D036104:Receptor, EphA2 / Q000378:metabolism; D012509:Sarcoma / Q000201:enzymology* / Q000378:metabolism
chemical_list: D007527:Isoenzymes; D011518:Proto-Oncogene Proteins; D036104:Receptor, EphA2; C490429:ACP1 protein, human; C490428:Acp1 protein, mouse; D017027:Protein Tyrosine Phosphatases