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: Paola Chiarugi, Maria Letizia Taddei, Nicola Schiavone, Laura Papucci, Elisa Giannoni, Tania Fiaschi, Sergio Capaccioli, Giovanni Raugei, Giampietro Ramponi
• Journal: Oncogene (Oncogene) Vol. 23 Issue 22 Pg. 3905-14 (May 13 2004) ISSN: 0950-9232 [Print] England
• PMID: 15021900 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Isoenzymes
• Proto-Oncogene Proteins
• Receptor, EphA2
• ACP1 protein, human
• Acp1 protein, mouse
• Protein Tyrosine Phosphatases

Topics

• Animals
• Isoenzymes (metabolism)
• Mice
• Mice, Nude
• NIH 3T3 Cells
• Neoplasms (enzymology, metabolism)
• Protein Tyrosine Phosphatases (metabolism)
• Proto-Oncogene Proteins
• Receptor, EphA2 (metabolism)
• Sarcoma (enzymology, metabolism)