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- Title
LMW-PTP is a positive regulator of tumor onset and growth.
- Authors
Chiarugi, Paola; Taddei, Maria Letizia; Schiavone, Nicola; Papucci, Laura; Giannoni, Elisa; Fiaschi, Tania; Capaccioli, Sergio; Raugei, Giovanni; Ramponi, Giampietro
- 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 ß-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 ß-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.
- Subjects
TUMOR growth; PROTEIN-tyrosine phosphatase; MOLECULAR weights; CELL adhesion; PHOSPHORYLATION; CELL proliferation
- Publication
Oncogene, 2004, Vol 23, Issue 22, p3905
- ISSN
0950-9232
- Publication type
Article
- DOI
10.1038/sj.onc.1207508