{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T22:53:41Z","timestamp":1773356021758,"version":"3.50.1"},"reference-count":37,"publisher":"Springer Science and Business Media LLC","issue":"7","license":[{"start":{"date-parts":[[1999,7,1]],"date-time":"1999-07-01T00:00:00Z","timestamp":930787200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nat Med"],"published-print":{"date-parts":[[1999,7]]},"DOI":"10.1038\/10533","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T08:43:33Z","timestamp":1027673013000},"page":"810-816","source":"Crossref","is-referenced-by-count":784,"title":["Blockade of the MAP kinase pathway suppresses growth of colon tumors in vivo"],"prefix":"10.1038","volume":"5","author":[{"given":"Judith S.","family":"Sebolt-Leopold","sequence":"first","affiliation":[]},{"given":"David T.","family":"Dudley","sequence":"additional","affiliation":[]},{"given":"Roman","family":"Herrera","sequence":"additional","affiliation":[]},{"given":"Keri Van","family":"Becelaere","sequence":"additional","affiliation":[]},{"given":"Amy","family":"Wiland","sequence":"additional","affiliation":[]},{"given":"Richard C.","family":"Gowan","sequence":"additional","affiliation":[]},{"given":"Haile","family":"Tecle","sequence":"additional","affiliation":[]},{"given":"Stephen D.","family":"Barrett","sequence":"additional","affiliation":[]},{"given":"Alexander","family":"Bridges","sequence":"additional","affiliation":[]},{"given":"Sally","family":"Przybranowski","sequence":"additional","affiliation":[]},{"given":"W.R.","family":"Leopold","sequence":"additional","affiliation":[]},{"given":"Alan R.","family":"Saltiel","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[1999,7,1]]},"reference":[{"key":"BFnm0799810_CR1","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1016\/S0065-230X(08)60765-4","volume":"74","author":"TS Lewis","year":"1998","unstructured":"Lewis, T.S., Shapiro, P.S. & Ahn, N.G. Signal transduction through MAP kinase cascades. Adv.Cancer Res. 74, 49\u2013139 (1998).","journal-title":"Adv.Cancer Res."},{"key":"BFnm0799810_CR2","doi-asserted-by":"publisher","first-page":"14843","DOI":"10.1074\/jbc.270.25.14843","volume":"270","author":"MH Cobb","year":"1995","unstructured":"Cobb, M.H. & Goldsmith, E.J. How MAP kinases are regulated. J. Biol. Chem. 270, 14843\u2013 14846 (1995).","journal-title":"J. Biol. Chem."},{"key":"BFnm0799810_CR3","doi-asserted-by":"publisher","first-page":"352","DOI":"10.1038\/364352a0","volume":"364","author":"PH Warne","year":"1993","unstructured":"Warne, P.H., Viciana, P.R. & Downward, J. Direct interaction of Ras and the amino-terminal region of Raf-1 in vitro. Nature 364, 352\u2013355 (1993).","journal-title":"Nature"},{"key":"BFnm0799810_CR4","doi-asserted-by":"publisher","first-page":"1404","DOI":"10.1126\/science.1326789","volume":"257","author":"P Dent","year":"1992","unstructured":"Dent, P. et al. Activation of mitogen-activated protein kinase kinase by v-Raf in NIH 3T3 cells and in vitro. Science 257, 1404\u20131407 (1992).","journal-title":"Science"},{"key":"BFnm0799810_CR5","doi-asserted-by":"publisher","first-page":"478","DOI":"10.1126\/science.1411546","volume":"258","author":"CM Crews","year":"1992","unstructured":"Crews, C.M., Alessandrini, A. & Erikson, R.L. The primary structure of MEK, a protein kinase that phosphorylates the ERK gene product. Science 258, 478\u2013480 (1992).","journal-title":"Science"},{"key":"BFnm0799810_CR6","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1042\/bj2960025","volume":"296","author":"JH Her","year":"1993","unstructured":"Her, J.H. et al. Dual phosphorylation and autophosphorylation in mitogen-activated protein (MAP) kinase activation. Biochem. J. 296, 25\u201331 (1993).","journal-title":"Biochem. J."},{"key":"BFnm0799810_CR7","doi-asserted-by":"publisher","first-page":"651","DOI":"10.1038\/343651a0","volume":"343","author":"NG Anderson","year":"1990","unstructured":"Anderson, N.G., Maller, J.L., Tonks, N.K. & Sturgill, T.W. Requirement for integration of signals from two distinct phosphorylation pathways for activation of MAP kinase. Nature 343, 651\u2013653 (1990).","journal-title":"Nature"},{"key":"BFnm0799810_CR8","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1016\/0092-8674(93)90237-K","volume":"73","author":"R Marais","year":"1993","unstructured":"Marais, R., Wynne, J. & Treisman, R. The SRF accessory protein Elk-1 contains a growth factor-regulated transcriptional activation domain. Cell 73, 381\u2013393 (1993).","journal-title":"Cell"},{"key":"BFnm0799810_CR9","doi-asserted-by":"publisher","first-page":"13585","DOI":"10.1074\/jbc.270.23.13585","volume":"270","author":"L Pang","year":"1995","unstructured":"Pang, L., Sawada, T., Decker, S.J. & Saltiel, A.R. Inhibition of MAP kinase kinase blocks the differentiation of PC-12 cells induced by nerve growth factor. J. Biol. Chem. 270, 13585\u201313588 (1995).","journal-title":"J. Biol. Chem."},{"key":"BFnm0799810_CR10","doi-asserted-by":"publisher","first-page":"841","DOI":"10.1016\/0092-8674(94)90133-3","volume":"77","author":"S Cowley","year":"1994","unstructured":"Cowley, S., Paterson, H., Kemp, P. & Marshall, C.J. Activation of MAP kinase kinase is necessary and sufficient for PC12 differentiation and for transformation of NIH3T3 cells. Cell 77, 841\u2013852 (1994).","journal-title":"Cell"},{"key":"BFnm0799810_CR11","doi-asserted-by":"crossref","first-page":"14373","DOI":"10.1016\/S0021-9258(19)49722-6","volume":"267","author":"R Seger","year":"1992","unstructured":"Seger, R. et al. Purification and characterization of mitogen-activated protein kinase activator(s) from epidermal growth factor-stimulated A431 cells. J. Biol. Chem. 267, 14373\u201314381 (1992).","journal-title":"J. Biol. Chem."},{"key":"BFnm0799810_CR12","doi-asserted-by":"publisher","first-page":"966","DOI":"10.1126\/science.8052857","volume":"265","author":"SJ Mansour","year":"1994","unstructured":"Mansour, S.J. et al. Transformation of mammalian cells by constitutively active MAP kinase kinase. Science 265, 966\u2013 970 (1994).","journal-title":"Science"},{"key":"BFnm0799810_CR13","unstructured":"Dudley, D.T. & Saltiel, A.R. in Signal Transduction, Cell Cycle and Their Inhibitors (ed. Gutkind, J.S.)(Humana, Totowa, New Jersey, in the press)."},{"key":"BFnm0799810_CR14","doi-asserted-by":"publisher","first-page":"7686","DOI":"10.1073\/pnas.92.17.7686","volume":"92","author":"DT Dudley","year":"1995","unstructured":"Dudley, D.T., Pang, L., Decker, S.J., Bridges, A.J. & Saltiel, A.R. A synthetic inhibitor of the mitogen-activated protein kinase cascade. Proc. Natl. Acad. Sci. USA 92, 7686\u20137689 (1995).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"BFnm0799810_CR15","doi-asserted-by":"publisher","first-page":"27489","DOI":"10.1074\/jbc.270.46.27489","volume":"270","author":"DR Alessi","year":"1995","unstructured":"Alessi, D.R., Cuenda, A., Cohen, P., Dudley, D.T. & Saltiel, A.R. PD 098059 is a specific inhibitor of the activation of mitogen-activated protein kinase kinase in vitro and in vivo. J. Biol. Chem. 270, 27489\u2013 27494 (1995).","journal-title":"J. Biol. Chem."},{"key":"BFnm0799810_CR16","doi-asserted-by":"publisher","first-page":"8319","DOI":"10.1073\/pnas.90.18.8319","volume":"90","author":"G Pages","year":"1993","unstructured":"Pages, G. et al. Mitogen-activated protein kinases p42mapk and p44mapk are required for fibroblast proliferation. Proc. Natl. Acad. Sci USA 90, 8319\u20138323 (1993).","journal-title":"Proc. Natl. Acad. Sci USA"},{"key":"BFnm0799810_CR17","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1007\/BF00196578","volume":"74","author":"M Streit","year":"1996","unstructured":"Streit, M., Schmidt, R., Hilgenfeld, R.U., Thiel, E. & Kreuser, E.D. Adhesion receptors in malignant transformation and dissemination of gastrointestinal tumors. J. Mol. Med. 74, 253\u2013268 (1996).","journal-title":"J. Mol. Med."},{"key":"BFnm0799810_CR18","doi-asserted-by":"publisher","first-page":"1110","DOI":"10.1128\/MCB.15.2.1110","volume":"15","author":"AJ Ridley","year":"1995","unstructured":"Ridley, A.J., Comoglio, P.M. & Hall, A. Regulation of scatter factor\/hepatocyte growth factor responses by Ras, Rac and Rho in MDCK cells. Mol. Cell Biol. 15, 1110\u20131122 (1995).","journal-title":"Mol. Cell Biol."},{"key":"BFnm0799810_CR19","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1242\/jcs.111.8.1039","volume":"111","author":"R Herrera","year":"1998","unstructured":"Herrera, R. Modulation of hepatocyte growth factor-induced scattering of HT29 colon carcinoma cells. Involvement of the MAPK pathway. J. Cell Science 111, 1039\u20131049 (1998).","journal-title":"J. Cell Science"},{"key":"BFnm0799810_CR20","doi-asserted-by":"publisher","first-page":"2185","DOI":"10.1091\/mbc.9.8.2185","volume":"9","author":"S Potempa","year":"1998","unstructured":"Potempa, S. & Ridley, A.J. Activation of both MAP kinase and phosphatidylinositide 3-kinase by Ras is required for hepatocyte growth factor\/scatter factor-induced adherens junction disassembly. Mol. Biol. Cell 9, 2185\u20132200 (1998).","journal-title":"Mol. Biol. Cell"},{"key":"BFnm0799810_CR21","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1038\/sj.onc.1201905","volume":"17","author":"S Tanimura","year":"1998","unstructured":"Tanimura, S. et al. Activation of the 41\/43 kDa mitogen-activated protein kinase signaling pathway is required for hepatocyte growth factor-induced cell scattering. Oncogene 17, 57\u201365 (1998).","journal-title":"Oncogene"},{"key":"BFnm0799810_CR22","doi-asserted-by":"publisher","first-page":"8773","DOI":"10.1073\/pnas.95.15.8773","volume":"95","author":"CP Webb","year":"1998","unstructured":"Webb, C.P., Van Aelst, L., Wigler, M.H. & Vande Woude, G.F. Signaling pathways in Ras-mediated tumorigenicity and metastasis. Proc. Natl. Acad. Sci. USA 95, 8773\u2013 8778 (1998).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"BFnm0799810_CR23","doi-asserted-by":"publisher","first-page":"18793","DOI":"10.1074\/jbc.273.30.18793","volume":"273","author":"A Khwaja","year":"1998","unstructured":"Khwaja, A., Lehmann, K., Marte, B.M. & Downward, J. Phosphoinositide 3-kinase induces scattering and tubulogenesis in epithelial cells through a novel pathway. J. Biol. Chem. 273, 18793\u201318801 (1998).","journal-title":"J. Biol. Chem."},{"key":"BFnm0799810_CR24","doi-asserted-by":"publisher","first-page":"4109","DOI":"10.1128\/MCB.18.7.4109","volume":"18","author":"M Takahashi-Tezuka","year":"1998","unstructured":"Takahashi-Tezuka, M. et al. Gab1 acts as an adapter molecule linking the cytokine receptor gp130 to ERK mitogen-activated protein kinase. Mol. Cell. Biol. 18, 4109\u20134117 (1998).","journal-title":"Mol. Cell. Biol."},{"key":"BFnm0799810_CR25","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1038\/384173a0","volume":"384","author":"KM Weidner","year":"1996","unstructured":"Weidner, K.M. et al. Interaction between Gab1 and the c-Met receptor tyrosine kinase is responsible for epithelial morphogenesis. Nature 384, 173\u2013176 (1996).","journal-title":"Nature"},{"key":"BFnm0799810_CR26","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1083\/jcb.137.2.481","volume":"137","author":"RL Klemke","year":"1997","unstructured":"Klemke, R.L. et al. Regulation of cell motility by mitogen-activated protein kinase. J. Cell Biol. 137, 481\u2013 492 (1997).","journal-title":"J. Cell Biol."},{"key":"BFnm0799810_CR27","first-page":"2434","volume":"35","author":"TH Corbett","year":"1975","unstructured":"Corbett, T.H., Griswold, D.P., Roberts, B.J., Peckham, J.C. & Schabel, F.M. Tumor induction relationships in development of transplantable cancers of the colon in mice for chemotherapy assays with a note on carcinogen structure. Cancer Res. 35, 2434\u20132439 (1975).","journal-title":"Cancer Res."},{"key":"BFnm0799810_CR28","doi-asserted-by":"publisher","first-page":"1478","DOI":"10.1172\/JCI119309","volume":"99","author":"VS Sivaraman","year":"1997","unstructured":"Sivaraman, V.S., Wang, H., Nuovo, G.J. & Malbon, C.C. Hyperexpression of mitogen-activated protein kinase in human breast cancer. J. Clin. Invest. 99, 1478\u20131483 (1997).","journal-title":"J. Clin. Invest."},{"key":"BFnm0799810_CR29","doi-asserted-by":"publisher","first-page":"1411","DOI":"10.1016\/S0002-9440(10)65728-8","volume":"153","author":"JW Mandell","year":"1998","unstructured":"Mandell, J.W., Hussaini, I.M., Zecevic, M., Weber, M.J. & VandenBerg, S.R. In situ visualization of intratumor growth factor signaling. Immunohistochemical localization of activated ERK\/MAP kinase in glial neoplasms. Amer. J. Pathol. 153, 1411\u20131423 (1998).","journal-title":"Amer. J. Pathol."},{"key":"BFnm0799810_CR30","doi-asserted-by":"publisher","first-page":"813","DOI":"10.1038\/sj.onc.1202367","volume":"18","author":"R Hoshino","year":"1999","unstructured":"Hoshino, R. et al. Constitutive activation of the 41-\/43-kDa mitogen-activated protein kinase signaling pathway in human tumors. Oncogene 18, 813\u2013822 (1999).","journal-title":"Oncogene"},{"key":"BFnm0799810_CR31","doi-asserted-by":"publisher","first-page":"1589","DOI":"10.1053\/gast.1997.v113.pm9352861","volume":"113","author":"LL Licato","year":"1997","unstructured":"Licato, L.L. et al.In vivo activation of mitogen-activated protein kinases in rat intestinal neoplasia. Gastroenterology 113, 1589\u20131598 (1997).","journal-title":"Gastroenterology"},{"key":"BFnm0799810_CR32","doi-asserted-by":"publisher","first-page":"1454","DOI":"10.1023\/A:1018894227169","volume":"43","author":"LL Licato","year":"1998","unstructured":"Licato, L.L. & Brenner. D.A. Analysis of signaling protein kinases in human colon or colorectal carcinomas. Dig. Dis. Sci. 43, 1454\u20131464 (1998).","journal-title":"Dig. Dis. Sci."},{"key":"BFnm0799810_CR33","doi-asserted-by":"publisher","first-page":"1255","DOI":"10.1083\/jcb.140.5.1255","volume":"140","author":"BP Eliceiri","year":"1998","unstructured":"Eliceiri, B.P., Klemke R., Stromblad, S. & Cheresh, D.A. Integrin alphavbeta3 requirement for sustained mitogen-activated protein kinase activity during angiogenesis. J. Cell Biol. 140, 1255\u2013 1263 (1998).","journal-title":"J. Cell Biol."},{"key":"BFnm0799810_CR34","doi-asserted-by":"publisher","first-page":"18165","DOI":"10.1074\/jbc.273.29.18165","volume":"273","author":"J Milanini","year":"1998","unstructured":"Milanini, J., Vinals, F., Pouyssegur, J. & Pages, G. p42\/p44 MAP kinase module plays a key role in the transcriptional regulation of the vascular endothelial growth factor gene in fibroblasts. J. Biol. Chem. 273, 18165\u201318172 (1998).","journal-title":"J. Biol. Chem."},{"key":"BFnm0799810_CR35","first-page":"1523","volume":"151","author":"AM Petit","year":"1997","unstructured":"Petit, A.M. et al. Neutralizing antibodies against epidermal growth factor and ErbB-2\/neu receptor tyrosine kinases down-regulate vascular endothelial growth factor production by tumor cells in vitro and in vivo: angiogenic implications for signal transduction therapy of solid tumors. Am. J. Pathol. 151, 1523\u20131530 (1997).","journal-title":"Am. J. Pathol."},{"key":"BFnm0799810_CR36","doi-asserted-by":"publisher","first-page":"2803","DOI":"10.1038\/sj.onc.1201815","volume":"16","author":"RJ Fiddes","year":"1998","unstructured":"Fiddes, R.J. et al. Inhibition of the MAP kinase cascade blocks heregulin-induced cell cycle progression in T-47D human breast cancer cells. Oncogene 16, 2803\u20132813 (1998).","journal-title":"Oncogene"},{"key":"BFnm0799810_CR37","doi-asserted-by":"publisher","first-page":"737","DOI":"10.1038\/sj.onc.1201829","volume":"16","author":"LT Amundadottir","year":"1998","unstructured":"Amundadottir, L.T. & Leder, P. Signal transduction pathways activated and required for mammary carcinogenesis in response to specific oncogenes. Oncogene 16, 737\u2013 746 (1998).","journal-title":"Oncogene"}],"container-title":["Nature Medicine"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/nm0799_810.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/nm0799_810","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/doifinder\/10.1038\/10533","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"},{"URL":"http:\/\/www.nature.com\/articles\/nm0799_810.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,12,1]],"date-time":"2021-12-01T20:44:35Z","timestamp":1638391475000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/nm0799_810"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1999,7]]},"references-count":37,"journal-issue":{"issue":"7","published-print":{"date-parts":[[1999,7]]}},"alternative-id":["BFnm0799810"],"URL":"https:\/\/doi.org\/10.1038\/10533","relation":{},"ISSN":["1078-8956","1546-170X"],"issn-type":[{"value":"1078-8956","type":"print"},{"value":"1546-170X","type":"electronic"}],"subject":[],"published":{"date-parts":[[1999,7]]}}}