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The rat tyrosine phosphatase η increases cell adhesion by activating c-Src through dephosphorylation of its inhibitory phosphotyrosine residue

Oncogene volume 24, pages 3187–3195 (2005)Cite this article

A Corrigendum to this article was published on 18 July 2016

Abstract

The expression of the receptor protein tyrosine phosphatase r-PTPη is drastically reduced in rat and human malignant thyroid cells, whereas its restoration reverts the neoplastic phenotype of retrovirally transformed rat thyroid cells. Moreover, reduced levels and loss of heterozygosity of DEP-1, the human homolog of r-PTPη, have been found in many human neoplasias. Here, we report that the r-PTPη protein binds to c-Src in living cells and dephosphorylates the c-Src inhibitory tyrosine phosphorylation site (Tyr 529), thereby increasing c-Src tyrosine kinase activity in malignant rat thyroid cells stably transfected with r-PTPη. Tyrosine phosphorylation of focal adhesion kinase (FAK) and paxillin was enhanced in r-PTPη-expressing cells. This was associated with increased adhesion of malignant r-PTPη-transfected thyroid cells vs both untransfected cells and cells stably transfected with an inactive r-PTPη mutant. Treatment of rat thyroid cells with the c-Src inhibitor PP2 decreased cell adhesion to a higher extent in r-PTPη-transfected cells than in mock-transfected or stably transfected cells with the inactive r-PTPη mutant, indicating that r-PTPη regulates cell–substratum adhesion by activating c-Src. Interestingly, the extent of both c-Src dephosphorylation at Tyr 529, FAK and paxillin phosphorylation, and the increased cell adhesion were associated with the degree of r-PTPη expression.

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References

  • Arregui CO, Balsamo J and Lilien J . (1998). J. Cell Biol., 143, 861–873.

  • Baker JE, Majeti R, Tangye SG and Weiss A . (2001). Mol. Cell Biol., 21, 2393–2403.

  • Bjorge JD, Jakymiw A and Fujita DJ . (2000). Oncogene, 19, 5620–5635.

  • Burridge K, Turner CE and Romer LH . (1992). J. Cell Biol., 119, 893–903.

  • Calalb MB, Polte TR and Hanks SK . (1995). Mol. Cell Biol., 15, 954–963.

  • Chiang GG and Sefton BM . (2000). J. Biol. Chem., 275, 6055–6058.

  • de la Fuente-Garcia MA, Nicolas JM, Freed JH, Palou E, Thomas AP, Vilella R, Vives J and Gaya A . (1998). Blood, 91, 2800–2809.

  • Florio T, Arena S, Thellung S, Iuliano R, Corsaro A, Massa A, Pattarozzi A, Bajetto A, Trapasso F, Fusco A and Schettini G . (2001). Mol. Endocrinol., 15, 1838–1852.

  • Fusco A, Berlingieri MT, Di Fiore PP, Portella G, Grieco M and Vecchio G . (1987). Mol. Cell Biol., 7, 3365–3370.

  • Fusco A, Portella G, Di Fiore PP, Berlingieri MT, Di Lauro R, Schneider AB and Vecchio G . (1985). J. Virol., 56, 284–292.

  • Guan JL and Shalloway D . (1992). Nature, 358, 690–692.

  • Hanks SK, Calalb MB, Harper MC and Patel SK . (1992). Proc. Natl. Acad. Sci. USA, 89, 8487–8491.

  • Harder KW, Moller NPH, Peacock JW and Jirik FR . (1998). J. Biol. Chem., 273, 31890–31900.

  • Holsinger LJ, Ward K, Duffield B, Zachwieja J and Jallal B . (2002). Oncogene, 21, 7067–7076.

  • Iuliano R, Le Pera I, Cristofaro C, Baudi F, Arturi F, Pallante P, Martelli ML, Trapasso F, Chiariotti L and Fusco A . (2004). Oncogene, 23, 8432–8438.

  • Iuliano R, Trapasso F, Le Pera I, Schepis F, Samà I, Clodomiro A, Dumon KR, Santoro M, Chiariotti L, Viglietto G and Fusco A . (2003). Cancer Res., 63, 882–886.

  • Iuliano R, Trapasso F, Samà I, Le Pera I, Martelli ML, Lembo F, Santoro M, Viglietto G, Chiariotti L and Fusco A . (2001). FEBS Lett., 500, 41–44.

  • Jandt E, Denner K, Kovalenko M, Ostman A and Bohmer FD . (2003). Oncogene, 22, 4175–4185.

  • Jones RJ, Avizienyte E, Wyke AW, Owens DW, Brunton VG and Frame MC . (2002). Br. J. Cancer, 87, 1128–1135.

  • Kaplan KB, Swedlow JR, Morgan DO and Varmus HE . (1995). Genes Dev., 9, 1505–1517.

  • Keane MM, Lowrey GA, Ettenberg SA, Dayton MA and Lipkowitz S . (1996). Cancer Res., 56, 4236–4243.

  • Kornberg L, Earp HS, Parsons JT, Schaller M and Juliano RL . (1992). J. Biol. Chem., 267, 23439–23442.

  • Kovalenko M, Denner K, Sandstrom J, Persson C, Gross S, Jandt E, Vilella R, Bohmer F and Ostman A . (2000). J. Biol. Chem., 275, 16219–16226.

  • Lampugnani MG, Zanetti A, Corada M, Takahashi T, Balconi G, Breviario F, Orsenigo F, Cattelino A, Kemler R, Daniel TO and Dejana E . (2003). J. Cell Biol., 161, 793–804.

  • Li L, Okura M and Imamoto A . (2002). Mol. Cell Biol., 22, 1203–1217.

  • Massa A, Barbieri F, Aiello C, Arena S, Pattarozzi A, Pirani P, Corsaro A, Iuliano R, Fusco A, Zona G, Spaziante R, Florio T and Schettini G . (2004). J. Biol. Chem., 279, 29004–29012.

  • Martelli ML, Trapasso F, Bruni P, Berlingieri MT, Battaglia C, Vento MT, Belletti B, Iuliano R, Santoro M, Viglietto G and Fusco A . (1998). Exp. Cell Res., 245, 195–202.

  • Nada S, Okada M, MacAuley A, Cooper JA and Nakagawa H . (1991). Nature, 351, 69–72.

  • Ostman A, Yang Q and Tonks NK . (1994). Proc. Natl. Acad. Sci. USA, 91, 9680–9684.

  • Palka HL, Park M and Tonks NK . (2003). J. Biol. Chem., 278, 5728–5735.

  • Petrone A and Sap J . (2000). J. Cell Sci., 113, 2345–2354.

  • Roussel RR, Brodeur SR, Shalloway D and Laudano AP . (1991). Proc. Natl. Acad. Sci. USA, 88, 10696–10700.

  • Ruivenkamp C, Hermsen M, Postma C, Klous A, Baak J, Meijer G and Demant P . (2003). Oncogene, 22, 3472–3474.

  • Ruivenkamp CA, van Wezel T, Zanon C, Stassen AP, Vlcek C, Csikos T, Klous AM, Tripodis N, Perrakis A, Boerrigter L, Groot PC, Lindeman J, Mooi WJ, Meijjer GA, Scholten G, Dauwerse H, Paces V, van Zandwijk N, van Ommen GJ and Demant P . (2002). Nat. Genet., 31, 295–300.

  • Schaller MD, Borgman CA, Cobb BS, Vines RR, Reynolds AB and Parsons JT . (1992). Proc. Natl. Acad. Sci. USA, 89, 5192–5196.

  • Smart JE, Oppermann H, Czernilofsky AP, Purchio AF, Erikson RL and Bishop JM . (1981). Proc. Natl. Acad. Sci. USA, 78, 6013–6017.

  • Tangye SG, Wu J, Aversa G, de Vries JE, Lanier LL and Phillips JH . (1998). J. Immunol., 161, 3803–3807.

  • Thomas SM, Soriano P and Imamoto A . (1995). Nature, 376, 267–271.

  • Tonks NK and Neel BG . (1996). Cell, 87, 365–368.

  • Trapasso F, Iuliano R, Boccia A, Stella A, Visconti R, Bruni P, Baldassarre G, Santoro M, Viglietto G and Fusco A . (2000). Mol. Cell Biol., 20, 9236–9246.

  • Trapasso F, Yendamuri S, Dumon KR, Iuliano R, Cesari R, Feig B, Seto R, Infante L, Ishii H, Vecchione A, During MJ, Croce CM and Fusco A . (2004). Carcinogenesis, 25, 2107–2114.

  • Xu W, Harrison SC and Eck MJ . (1997). Nature, 385, 595–602.

  • Zheng XM, Resnick RJ and Shalloway D . (2000). EMBO J., 19, 964–978.

  • Zhang L, Martelli ML, Battaglia C, Trapasso F, Tramontano D, Viglietto G, Porcellini A, Santoro M and Fusco A . (1997). Exp. Cell Res., 235, 62–70.

  • Zimmermann P, Tomatis D, Rosas M, Grootjans J, Leenaerts I, Degeest G, Reekmans G, Coomans C and David G . (2001). Mol. Biol. Cell, 12, 339–350.

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Acknowledgements

We thank Antonio Brunetti for technical and scientific advice. We are grateful to Jean Gilder for editing the text. This work was supported by grants from the Associazione Italiana Ricerca sul Cancro (AIRC), the Consiglio Nazionale delle Ricerche, the Ministero dell'Università e della Ricerca Scientifica e Tecnologica (MIUR), ‘Piani di Potenziamento della Rete Scientifica e Tecnologica’ CLUSTER C-04 and the ‘Ministero della Salute’. We thank the Associazione Partenopea per le Ricerche Oncologiche (APRO) for its support. ILP is supported by a fellowship from AIRC.

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Author notes

  1. Ilaria Le Pera and Rodolfo Iuliano: These authors contributed equally to this study

Authors and Affiliations

  1. Department of Experimental and Clinical Medicine, Medical School of Catanzaro, ‘Magna Graecia’ University of Catanzaro, 88100, Catanzaro, Italy

    Ilaria Le Pera, Rodolfo Iuliano, Francesco Trapasso, Lorenzo Chiariotti & Giuseppe Viglietto

  2. Department of Oncology, Biology and Genetics, University of Genova, 16132, Genova, Italy

    Tullio Florio & Gennaro Schettini

  3. INSERM U531, IFR 31,CHU Rangueil, 1 av. Jean Poulhès, 31403, Toulouse Cedex, France

    Christiane Susini

  4. Department of Biology and Molecular and Cellular Pathology, CNR Endocrinology and Experimental Oncology Center, Medical School, ‘Federico II’ University of Naples, 80131, Naples, Italy

    Massimo Santoro, Giuseppe Viglietto & Alfredo Fusco

  5. Department of S.pe.S., University of Molise, 86100, Campobasso, Italy

    Lorenzo Chiariotti

  6. NOGEC (Naples Oncogenomic Center)-CEINGE, 80145, Naples, Italy

    Alfredo Fusco

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  1. Ilaria Le Pera
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Correspondence to Alfredo Fusco.

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Pera, I., Iuliano, R., Florio, T. et al. The rat tyrosine phosphatase η increases cell adhesion by activating c-Src through dephosphorylation of its inhibitory phosphotyrosine residue. Oncogene 24, 3187–3195 (2005). https://doi.org/10.1038/sj.onc.1208510

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