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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References
Belfiore A, Gangemi P, Costantino A, Russo G, Santonocito GM, Ippolito O, Di Renzo MF, Comoglio P, Fiumara A, Vigneri R . 1997 J. Clin. Endocrinol. Metab. 82: 2322–2328
Bergstrom JD, Hermansson A, Diaz de Stahl T, Heldin NE . 1999 Br. J. Cancer. 80: 650–656
Bergstrom JD, Westermark B, Heldin NE . 2000 Exp. Cell Res. 259: 293–299
Birchmeier C, Gherardi E . 1998 Trends Cell. Biol. 8: 404–410
Brasher BB, Van Etten RA . 2000 J. Biol. Chem. 29: 35631–35637
Buchdunger E, Cioffi CL, Law N, Stover D, Ohno-Jones S, Druker BJ, Lydon NB . 2000 J. Pharmacol. Exp. Ther. 295: 139–145
Buchdunger E, Zimmermann J, Mett H, Meyer T, Muller M, Druker BJ, Lydon NB . 1996 Cancer Res. 56: 100–104
Di Renzo MF, Olivero M, Serini G, Orlandi F, Pilotti S, Belfiore A, Costantino A, Vigneri R, Angeli A, Pierotti MA. et al . 1995 J. Endocrinol. Invest. 18: 134–139
Druker BJ, Lydon NB . 2000 J Clin Invest. 105: 3–7. Review
Druker BJ, Tamura S, Buchdunger E, Ohno S, Segal GM, Fanning S, Zimmermann J, Lydon NB . 1996 Nat. Med. 2: 561–566
Giordano S, Zhen Z, Medico E, Gaudino G, Galimi F, Comoglio PM . 1993 Proc. Natl. Acad. Sci. USA 90: 649–653
Heinrich MC, Griffith DJ, Druker BJ, Wait CL, Ott KA, Zigler AJ . 2000 Blood 96: 925–932
Heldin NE, Cvejic D, Smeds S, Westermark B . 1991 Endocrinology 129: 2187–2193
Heldin NE, Gustavsson B, Claesson-Welsh L, Hammacher A, Mark J, Heldin CH, Westermark B . 1988 Proc. Natl. Acad. Sci. USA 85: 9302–9306
Jiang W, Hiscox S, Matsumoto K, Nakamura T . 1999 Crit. Rev. Oncol. Hematol. 29: 209–248
Kilic T, Alberta JA, Zdunek PR, Acar M, Iannarelli P, O'Reilly T, Buchdunger E, Black PM, Stiles CD . 2000 Cancer Res. 60: 5143–5150
Kjoller L, Hall A . 1999 Exp. Cell Res. 253: 166–179
Krystal GW, Honsawek S, Litz J, Buchdunger E . 2000 Clin. Cancer Res. 6: 3319–3326
Lanier LM, Gertler FB . 2000 Curr. Opin. Neurobiol. 10: 80–87
le Coutre P, Mologni L, Cleris L, Marchesi E, Buchdunger E, Giardini R, Formelli F, Gambacorti-Passerini C . 1999 J. Natl. Cancer Inst. 91: 163–168
Lewis JM, Baskaran R, Taagepera S, Schwartz MA, Wang JY . 1996 Proc. Natl. Acad. Sci. USA 93: 15174–15179
Natali PG, Berlingieri MT, Nicotra MR, Fusco A, Santoro E, Bigotti A, Vecchio G . 1995 Cancer Res. 55: 1787–1791
Nobes CD, Hall A . 1999 J. Cell. Biol. 144: 1235–1244
Parsons JT, Parsons SJ . 1997 Curr. Opin. Cell. Biol. 9: 187–192
Plattner R, Kadlec L, DeMali KA, Kazlauskas A, Pendergast AM . 1999 Genes Dev. 13: 2400–2411
Schindler T, Bornmann W, Pellicena P, Miller WT, Clarkson B, Kuriyan J . 2000 Science 289: 1938–1942
Sieg DJ, Hauck CR, Ilic D, Klingbeil CK, Schaefer E, Damsky CH, Schlaepfer DD . 2000 Nat. Cell. Biol. 2: 249–256
Sieg DJ, Ilic D, Jones KC, Damsky CH, Hunter T, Schlaepfer DD . 1998 EMBO J. 17: 5933–5947
Stuart KA, Riordan SM, Lidder S, Crostella L, Williams R, Skouteris GG . 2000 Int. J. Exp. Pathol. 81: 17–30
Tanaka T, Umeki K, Yamamoto I, Kotani T, Sakamoto F, Noguchi S, Ohtaki S . 1995 Endocr. J. 42: 723–728
Trusolino L, Cavassa S, Angelini P, Ando M, Bertotti A, Comoglio PM, Boccaccio C . 2000 FASEB J. 14: 1629–1640
Wang WL, Healy ME, Sattler M, Verma S, Lin J, Maulik G, Stiles CD, Griffin JD, Johnson BE, Salgia R . 2000 Oncogene 19: 3521–3528
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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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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DOI: https://doi.org/10.1038/sj.onc.1204531
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