[PTPL1, a proapoptotic protein tyrosine phosphatase in breast cancers].
The protein tyrosine phosphatase L1 (PTPL1), also known as FAP1, has two major types of remarkable structural domains, in addition to its catalytic unit: a FERM domain which is responsible for its localization at the apical pole of the cell plasma membrane and 5 PDZ domains suggestive of numerous possibilities of protein partners and consequently of a role as a cargo protein or an integrator between different signalling pathways. In fact, though it was initially suggested, in 1995, that this enzyme acts as an inhibitor of Fas death receptor several recent studies indicate that PTPL1 plays many other roles. It dephosphorylates Ephrin B (ligand of Eph, a receptor triggering angiogenesis and axonal guidance), it interacts with numerous proteins associated to cytoskeleton plasticity and it is implicated in cytokinesis. We have demonstrated that its expression is regulated by antiestrogens in mammary cancer and shown, with stable antisense transfectants, that PTPL1 plays a key role in the mediation of the inhibitory effects of these antagonists on growth factor signalling by impeding the IRS-I/PI3-K/Akt survival pathway. Altogether PTPL1 has to be regarded as a unique marker of mammary tumor response to antiestrogens and a potential therapeutic target to activate apoptotic stimuli in tumor cells.
Freiss
Gilles
G
Inserm U540, Endocrinologie moléculaire et cellulaire des cancers, 60, rue de Navacelles, 34090 Montpellier. freiss@u540.montp.inserm.fr
Bompard
Guillaume
G
Vignon
Françoise
F
D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000235:genetics* / Q000503:physiopathology*; D002470:Cell Survival; D003599:Cytoskeleton / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D054595:Protein Tyrosine Phosphatase, Non-Receptor Type 13; D017027:Protein Tyrosine Phosphatases / Q000235:genetics* / Q000494:pharmacology*; D015398:Signal Transduction
D014408:Biomarkers, Tumor; C516742:PTPN13 protein, human; D054595:Protein Tyrosine Phosphatase, Non-Receptor Type 13; D017027:Protein Tyrosine Phosphatases