Abstract
When aberrantly expressed or activated, the Met receptor tyrosine kinase is involved in tumor invasiveness and metastasis. In this study, we have used the Xenopus embryonic system to define the role of various Met proximal-binding partners and downstream signaling pathways in regulating an induced morphogenetic event. We show that expression of an oncogenic derivative of the Met receptor (Tpr-Met) induces ectopic morphogenetic structures during Xenopus embryogenesis. Using variant forms of Tpr-Met that are engineered to recruit a specific signaling molecule of choice, we demonstrate that the sole recruitment of either the Grb2 or the Shc adaptor protein is sufficient to induce ectopic structures and anterior reduction, while the recruitment of PI-3Kinase (PI-3K) is necessary but not sufficient for this effect. In contrast, the recruitment of PLCĪ³ can initiate the induction, but fails to maintain or elongate supernumerary structures. Finally, evidence indicates that the Ras/Raf/MAPK pathway is necessary, but not sufficient to induce these structures. This study also emphasizes the importance of examining signaling molecules in the regulatory context that is provided by receptor/effector interactions when assessing a role in cell growth and differentiation.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 50 print issues and online access
$259.00 per year
only $5.18 per issue
Buy this article
Purchase on Springer Link
Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
Accession codes
References
Aoki S, Takahashi K, Matsumoto K, Nakamura T . (1997). Biochem Biophys Res Commun 234: 8ā14.
Atabey N, Gao Y, Yao ZJ, Breckenridge D, Soon L, Soriano JV et al. (2001). J Biol Chem 276: 14308ā14314.
Bardelli A, Basile ML, Audero E, Giordano S, Wennstrom S, Menard S et al. (1999). Oncogene 18: 1139ā1146.
Bardelli A, Longati P, Gramaglia D, Stella MC, Comoglio PM . (1997). Oncogene 15: 3103ā3111.
Bellusci S, Moens G, Gaudino G, Comoglio P, Nakamura T, Thiery JP et al. (1994). Oncogene 9: 1091ā1099.
Berthou S, Aebersold DM, Schmidt LS, Stroka D, Heigl C, Streit B et al. (2004). Oncogene 23: 5387ā5393.
Brewster R, Mullor JL, Ruiz i Altaba A . (2000). Development 127: 4395ā4405.
Cacace AM, Michaud NR, Therrien M, Mathes K, Copeland T, Rubin GM et al. (1999). Mol Cell Biol 19: 229ā240.
Carballada R, Yasuo H, Lemaire P . (2001). Development 128: 35ā44.
Chen P, Xie H, Wells A . (1996). Mol Biol Cell 7: 871ā881.
Chen Y, Holleman T, Grunz H, Pieler T . (1999). Mech Dev 80: 67ā76.
Cheng AM, Saxton TM, Sakai R, Kulkarni S, Mbamalu G, Vogel W et al. (1998). Cell 95: 793ā803.
Ciruna BG, Schwartz L, Harpal K, Yamaguchi TP, Rossant J . (1997). Development 124: 2829ā2841.
Christen B, Beck CW, Lombardo A, Slack JM . (2003). Dev Dyn 226: 349ā355.
Christensen JG, Burrows J, Salgia R . (2005). Cancer Lett 225: 1ā26.
Christensen JG, Schreck R, Burrows J, Kuruganti P, Chan E, Le P et al. (2003). Cancer Res 63: 7345ā7355.
Chong LD, Park EK, Latimer E, Friesel R, Daar IO . (2000). Mol Cell Biol 20: 724ā734.
Coltella N, Manara MC, Cerisano V, Trusolino L, Di Renzo MF, Scotlandi K et al. (2003). FASEB J 17: 1162ā1164.
Danilkovitch-Miagkova A, Zbar B . (2002). J Clin Invest 109: 863ā867.
Dean M, Park M, Vande Woude GF . (1987). Mol Cell Biol 7: 921ā924.
Di Renzo MF, Olivero M, Ferro S, Prat M, Bongarzone I, Pilotti S et al. (1992). Oncogene 7: 2549ā2553.
Dupont H, Blancq M . (1999). Eur J Biochem 265: 530ā538.
Fabian JR, Morrison DK, Daar IO . (1993). J Cell Biol 122: 645ā652.
Fixman ED, Fournier TM, Kamikura DM, Naujokas MA, Park M . (1996). J Biol Chem 271: 13116ā13122.
Fixman ED, Holgado-Madruga M, Nguyen L, Kamikura DM, Fournier TM, Wong AJ et al. (1997). J Biol Chem 272: 20167ā20172.
Fixman ED, Naujokas MA, Rodrigues GA, Moran MF, Park M . (1995). Oncogene 10: 237ā249.
Furge KA, Zhang YW, Vande Woude GF . (2000). Oncogene 19: 5582ā5589.
Gao CF, Vande Woude GF . (2005). Cell Res 15: 49ā51.
Gupta RW, Mayer BJ . (1998). Oncogene 17: 2155ā2165.
Gurdon JB, Brennan S, Fairman S, Mohun TJ . (1984). Cell 38: 691ā700.
Hama J, Xu H, Goldfarb M, Weinstein DC . (2001). Mech Dev 109: 195ā204.
Harland R, Gerhart J . (1997). Annu Rev Cell Dev Biol 13: 611ā667.
Hemmati-Brivanlou A, Melton DA . (1994). Cell 77: 273ā281.
Homma Y, Takenawa Y . (1992). J Biol Chem 267: 21844ā21849.
Hopwood ND, Pluck A, Gurdon JB . (1989). EMBO J 8: 3409ā3417.
Jacobson M, Rutishauser U . (1986). Dev Biol 116: 524ā531.
Jeffers M, Koochekpour S, Fiscella M, Sathyanarayana BK, Vande Woude GF . (1998). Oncogene 17: 2691ā2700.
Jeffers M, Rong S, Anver M, Vande Woude GF . (1996). Oncogene 13: 853ā856.
Jeffers M, Schmidt L, Nakaigawa N, Webb CP, Weirich G, Kishida T et al. (1997). Proc Natl Acad Sci USA 94: 11445ā11450.
Kamikura DM, Khoury H, Maroun C, Naujokas MA, Park M . (2000). Mol Cell Biol 20: 3482ā3496.
Kamikura DM, Naujokas MA, Park M . (1996). Biochemistry 35: 1010ā1017.
Kang Y, Massague J . (2004). Cell 118: 277ā279.
Kim P, Helms AW, Johnson JE, Zimmerman K . (1997). Dev Biol 187: 1ā12.
Koibuchi N, Kaneda Y, Taniyama Y, Matsumoto K, Nakamura T, Ogihara T et al. (2004). Blood 103: 3320ā3325.
LaBonne C, Burke B, Whitman M . (1995). Development 121: 1475ā1486.
LaBonne C, Whitman M . (1994). Development 120: 463ā472.
Lengyel E, Prechtel D, Resau JH, Gauger K, Welk A, Lindemann K et al. (2005). Int J Cancer 113: 678ā682.
Liu C, Park M, Tsao MS . (1992). Oncogene 7: 181ā185.
Lock LS, Frigault MM, Saucier C, Park M . (2003). J Biol Chem 278: 30083ā30090.
Lock LS, Royal I, Naujokas MA, Park M . (2000). J Biol Chem 275: 31536ā31545.
Lombardo A, Slack JM . (2001). Mech Dev 106: 191ā195.
MacNicol AM, Muslin AJ, Williams LT . (1993). Cell 73: 571ā583.
Maeda R, Mood K, Jones TL, Aruga J, Buchberg AM, Daar IO . (2001). Oncogene 20: 1329ā1342.
Maroun CR, Moscatello DK, Naujokas MA, Holgado-Madruga M, Wong AJ, Park M . (1999). J Biol Chem 274: 31719ā31726.
Maulik G, Kijima T, Ma PC, Ghosh SK, Lin J, Shapiro GI et al. (2002). Clin Cancer Res 8: 620ā627.
Mayor R, Morgan R, Sargent MG . (1995). Development 121: 767ā777.
Mood K, Saucier C, Ishimura A, Bong Y-S, Lee H-S, Park M et al. (2005). J Cell Physiol 207: 271ā285.
Nakata K, Nagai T, Aruga J, Mikoshiba K . (1997). Proc Natl Acad Sci USA 94: 11980ā11985.
Nguyen L, Holgado-Madruga M, Maroun C, Fixman ED, Kamikura D, Fournier T et al. (1997). J Biol Chem 272: 20811ā20819.
Park EK, Warner N, Bong YS, Stapleton D, Maeda R, Pawson T et al. (2004). Mol Biol Cell 15: 1647ā1655.
Ponzetto C, Bardelli A, Zhen Z, Maina F, dalla Zonca P, Giordano S et al. (1994). Cell 77: 261ā271.
Ponzetto C, Zhen Z, Audero E, Maina F, Bardelli A, Basile ML et al. (1996). J Biol Chem 271: 14119ā14123.
Powers CJ, McLeskey SW, Wellstein A . (2000). Endocr Relat Cancer 7: 165ā197.
Pownall ME, Tucker AS, Slack JM, Isaacs HV . (1996). Development 122: 3881ā3892.
Radisky DC . (2005). J Cell Sci 118: 4325ā4326.
Rodrigues GA, Park M . (1993). Mol Cell Biol 13: 6711ā6722.
Rodrigues GA, Park M . (1994). Oncogene 9: 2019ā2027.
Rong S, Jeffers M, Resau JH, Tsarfaty I, Oskarsson M, Vande Woude GF . (1993). Cancer Res 53: 5355ā5360.
Rong S, Vande Woude GF . (1994). Cold Spring Harb Symp Quant Biol 59: 629ā636.
Sato SM, Sargent TD . (1991). Development 112: 747ā753.
Sattler M, Pride YB, Ma P, Gramlich JL, Chu SC, Quinnan LA et al. (2003). Cancer Res 63: 5462ā5469.
Saucier C, Papavasiliou V, Palazzo A, Naujokas MA, Kremer R, Park M . (2002). Oncogene 21: 1800ā1811.
Schmidt L, Junker K, Weirich G, Glenn G, Choyke P, Lubensky I et al. (1998). Cancer Res 58: 1719ā1722.
Shook D, Keller R . (2003). Mech Dev 120: 1351ā1383.
Sive HL, Grainger RM, Harland RM . (2000). In: Sive HL (ed). Early Development of Xenopus Laevis. A Laboratory Manual. Cold Spring Harbor Press: Cold Spring Harbor, NY, pp 143ā170.
Smith JC, Price BM, Green JB, Weigel D, Herrmann BG . (1991). Cell 67: 79ā87.
Stern CD, Ireland GW, Herrick SE, Gherardi E, Gray J, Perryman M et al. (1990). Development 110: 1271ā1284.
Stewart S, Sundaram M, Zhang Y, Lee J, Han M, Guan KL . (1999). Mol Cell Biol 19: 5523ā5534.
Tada M, O'Reilly MA, Smith JC . (1997). Development 124: 2225ā2234.
Takayama H, La Rochelle WJ, Anver M, Bockman DE, Merlino G . (1996). Proc Natl Acad Sci USA 93: 5866ā5871.
Takayama H, La Rochelle WJ, Sharp R, Otsuka T, Kriebel P, Anver M et al. (1997). Proc Natl Acad Sci USA 94: 701ā706.
Thiery JP . (2002). Nature Reviews Cancer 2: 442ā454.
To CT, Tsao MS . (1998). Oncol Rep 5: 1013ā1024.
Tsao MS, Zhu H, Giaid A, Viallet J, Nakamura T, Park M . (1993). Cell Growth Differ 4: 571ā579.
Tsarfaty I, Alvord WG, Resau JH, Altsock RT, Lidereau R, Bieche I et al. (1999). Anal Quant Cytol Histol 21: 397ā408.
Umbhauer M, Marshall CJ, Mason CS, Old RW, Smith JC . (1995). Nature 376: 58ā62.
Vernon AE, LaBonne C . (2004). Curr Biol 14: 719ā721.
Weidner KM, Di Cesare S, Sachs M, Brinkmann V, Behrens J, Birchmeier W . (1996). Nature 384: 173ā176.
Weinstein DC, Marden J, Carnevali F, Hemmati-Brivanlou A . (1998). Nature 394: 904ā908.
Whitman M, Melton DA . (1992). Nature 357: 252ā254.
Yang J, Mani SA, Donaher JL, Ramaswamy S, Itzykson RA, Come C et al. (2004). Cell 117: 927ā939.
Yasuo H, Lemaire P . (2001). Int J Dev Biol 45: 229ā235.
Zhang YW, Su Y, Volpert OV, Vande Woude GF . (2003). Proc Natl Acad Sci USA 100: 12718ā12723.
Acknowledgements
We thank Morag Park for helpful discussions, Deborah Morrison for DnKSR, Malcolm Whitman for RasN17, and Tom Sargent, Jonathan Slack, John Gurdon, Sally Moody, Christof Niehrs, I Dawid for in situ constructs. AI was supported by a Japan Society for the Promotion of Science Research Fellowship. This research was supported by the Intramural Research Program of the NIH, NCI.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Ishimura, A., Lee, HS., Bong, YS. et al. Oncogenic Met receptor induces ectopic structures in Xenopus embryos. Oncogene 25, 4286ā4299 (2006). https://doi.org/10.1038/sj.onc.1209463
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.onc.1209463