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  • Original Paper
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Tyrosine kinase inhibitor STI571 enhances thyroid cancer cell motile response to Hepatocyte Growth Factor

Oncogene volume 20, pages 3845–3856 (2001)Cite this article

Abstract

The Hepatocyte Growth Factor (HGF) and its receptor Met are physiological regulators of cell migration. HGF and Met have also been implicated in tumor progression and metastasis. We show here that the tyrosine kinase inhibitor STI571 has a stimulatory effect on HGF-induced migration and branching morphogenesis in thyroid cancer but not in primary or immortalized thyroid epithelial cells. These stimulatory effects of STI571 are observed at a concentration that is clinically relevant. The STI571-enhanced motile response can be correlated with an increase in the Met receptor tyrosine phosphorylation as well as ERK and Akt activation by HGF. Interestingly, one of the targets of STI571, namely the c-Abl tyrosine kinase, is activated by HGF and is recruited at the migrating edge of thyroid cancer cells. These data suggests that c-Abl and/or STI571-inhibited tyrosine kinases can negatively regulate the Met receptor to restrain the motile response in thyroid cancer cells.

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Acknowledgements

We thank Novartis for STI571. F Frasca is a recipient of a fellowship from Fondazione Italiana Ricerca sul Cancro (FIRC, Italy). These studies were supported by grants from the National Institute of Health (USA) to JYJ Wang (HL57900), and from Associazione Italiana Ricerca sul Cancro (AIRC) and Ministero dell‘Universita’ e della Ricerca Scientifica e Tecnologica (MURST, Italy) to R Vigneri.

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Authors and Affiliations

  1. Istituto di Medicina Interna, Malattie Endocrine e Del Metabolismo, Università di Catania, Ospedale Garibaldi, Piazza S. Maria di Gesù, 95123, Catania, Italy

    Francesco Frasca, Veronica Vella & Riccardo Vigneri

  2. Division of Biology, University of California, San Diego, 9500 Gilman Drive, La Jolla, 92093-0322, California, CA, USA

    Francesco Frasca, Paolo Vigneri & Jean Y J Wang

  3. Cancer Center, University of California, San Diego, 9500 Gilman Drive, La Jolla, 92093-0322, California, CA

    Francesco Frasca, Paolo Vigneri & Jean Y J Wang

  4. USA

    Francesco Frasca, Paolo Vigneri & Jean Y J Wang

  5. Dipartimento di Medicina Sperimentale e Clinica, Università degli Studi di Catanzaro, Magna Graecia, Via T. Campanella 115, 88100, Catanzaro, Italy

    Paolo Vigneri

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  1. Francesco Frasca
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Correspondence to Francesco Frasca or Jean Y J Wang.

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Frasca, F., Vigneri, P., Vella, V. et al. Tyrosine kinase inhibitor STI571 enhances thyroid cancer cell motile response to Hepatocyte Growth Factor. Oncogene 20, 3845–3856 (2001). https://doi.org/10.1038/sj.onc.1204531

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