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The tyrosine kinase Abl is required for Src-transforming activity in mouse fibroblasts and human breast cancer cells

Oncogene volume 26, pages 7313–7323 (2007)Cite this article

Abstract

The cytoplasmic tyrosine kinase Src has been implicated in signal transduction induced by growth factors and integrins. Src also shows oncogenic activity when deregulated. Accumulating evidence indicates that the tyrosine kinase Abl is an important substrate for Src signalling in normal cells. Here we show that Abl is also required for Src-induced transformation of mouse fibroblasts. Abl does not mediate tyrosine phosphorylation of Stat3 and Shc, two important regulators of Src oncogenic activity. In contrast, Abl controls the activation of the small GTPase Rac for oncogenic signalling and active Rac partly rescued Src transformation in cells with inactive Abl. Moreover, Abl mediates Src-induced extracellular regulated kinase 5 (ERK5) activation to drive cell transformation. Finally, we find that Abl/Rac and Abl/ERK5 pathways also operate in human MCF7 and BT549 breast cancer cells, where neoplastic transformation depends on Src-like activities. Therefore, Abl is an important regulator of Src oncogenic activity both in mouse fibroblasts and in human cancer cells. Targeting these Abl-dependent signalling cascades may be of therapeutic value in breast cancers where Src-like function is important.

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Acknowledgements

We thank K Ballmer-Hofer (Paul Scherrer Institute), XB Bustelo (University of Salamenca), SA Courtneidge (the Burnham Institute for Medical research), A Pandiella (University of Salamenca), J Raingeaud (INSERM U641) and B Willi (Novartis Pharma) for various reagents. We thank C Tournier (University of Manchester) and R Hipskind (CNRS UMR 5535) for constructs and helpful discussion, and our colleagues for critically reading the manuscript. This work was supported by the CNRS, ARC, AICR and INCa. AB was supported by AICR, CL by INCa, AS by Laboratoires Servier and SR by INSERM.

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  1. A Boureux

    Present address: 3Current address: IGH UPR1142-UMII, place Eugène Bataillon, 34095 Montpellier, France.,

  2. A Sirvent and A Boureux: These authors contributed equally to this work.

Authors and Affiliations

  1. CRBM, CNRS UMR5237 – UMII, 1919 route de Mende, Montpellier, France

    A Sirvent, A Boureux, V Simon, C Leroy & S Roche

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Correspondence to S Roche.

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Sirvent, A., Boureux, A., Simon, V. et al. The tyrosine kinase Abl is required for Src-transforming activity in mouse fibroblasts and human breast cancer cells. Oncogene 26, 7313–7323 (2007). https://doi.org/10.1038/sj.onc.1210543

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