PTPD1, a cytosolic non-receptor protein tyrosine phosphatase, stimulates the src-EGF transduction pathway. Localization of PTPD1 at actin cytoskeleton and adhesion sites is required for cell scattering and migration. Here, we show that during EGF stimulation PTPD1 is rapidly recruited to endocytic vesicles containing EGF receptor (EGFR). Endosomal localization of PTPD1 is mediated by interaction with KIF16B, an endosomal kinesin that modulates receptor recycling at the plasma membrane. Silencing of PTPD1 promotes degradation of EGF receptor and inhibits downstream ERK signaling. We also found that PTPD1 is markedly increased in bladder cancer tissue samples. PTPD1 levels positively correlated with the grading and invasiveness potential of these tumors. Transgenic expression of an inactive PTPD1 mutant or genetic knock-down of the endogenous PTPD1 severely inhibited both growth and motility of human bladder cancer cells. These findings identify PTPD1 as a novel component of the endocytic machinery that impacts on EGFR stability and on growth and motility of bladder cancer cells.

PTPD1 supports receptor stability and mitogenic signaling in bladder cancer cells.

GARBI, CORRADO;Galgani M.;MASCOLO, MASSIMO;QUARTO, MARIA;INSABATO, LUIGI;FELICIELLO, ANTONIO
2010

Abstract

PTPD1, a cytosolic non-receptor protein tyrosine phosphatase, stimulates the src-EGF transduction pathway. Localization of PTPD1 at actin cytoskeleton and adhesion sites is required for cell scattering and migration. Here, we show that during EGF stimulation PTPD1 is rapidly recruited to endocytic vesicles containing EGF receptor (EGFR). Endosomal localization of PTPD1 is mediated by interaction with KIF16B, an endosomal kinesin that modulates receptor recycling at the plasma membrane. Silencing of PTPD1 promotes degradation of EGF receptor and inhibits downstream ERK signaling. We also found that PTPD1 is markedly increased in bladder cancer tissue samples. PTPD1 levels positively correlated with the grading and invasiveness potential of these tumors. Transgenic expression of an inactive PTPD1 mutant or genetic knock-down of the endogenous PTPD1 severely inhibited both growth and motility of human bladder cancer cells. These findings identify PTPD1 as a novel component of the endocytic machinery that impacts on EGFR stability and on growth and motility of bladder cancer cells.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11588/371385
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