Activation of MEK1 or MEK2 isoform is sufficient to fully transform intestinal epithelial cells and induce the formation of metastatic tumors

go back to reference Markowitz SD, Dawson DM, Willis J, Willson JK: Focus on colon cancer. Cancer Cell. 2002, 1: 233-236. 10.1016/S1535-6108(02)00053-3.CrossRefPubMed Markowitz SD, Dawson DM, Willis J, Willson JK: Focus on colon cancer. Cancer Cell. 2002, 1: 233-236. 10.1016/S1535-6108(02)00053-3.CrossRefPubMed

go back to reference Fearon ER, Vogelstein B: A genetic model for colorectal tumorigenesis. Cell. 1990, 61: 759-767. 10.1016/0092-8674(90)90186-I.CrossRefPubMed Fearon ER, Vogelstein B: A genetic model for colorectal tumorigenesis. Cell. 1990, 61: 759-767. 10.1016/0092-8674(90)90186-I.CrossRefPubMed

go back to reference Schubbert S, Shannon K, Bollag G: Hyperactive Ras in developmental disorders and cancer. Nat Rev Cancer. 2007, 7: 295-308. 10.1038/nrc2109.CrossRefPubMed Schubbert S, Shannon K, Bollag G: Hyperactive Ras in developmental disorders and cancer. Nat Rev Cancer. 2007, 7: 295-308. 10.1038/nrc2109.CrossRefPubMed

go back to reference Andreyev HJ, Norman AR, Cunningham D, Oates J, Dix BR, Iacopetta BJ, Young J, Walsh T, Ward R, Hawkins N, Beranek M, Jandik P, Benamouzig R, Jullian E, Laurent-Puig P, Olschwang S, Muller O, Hoffmann I, Rabes HM, Zietz C, Troungos C, Valavanis C, Yuen ST, Ho JW, Croke CT, O'Donoghue DP, Giaretti W, Rapallo A, Russo A, Bazan V, Tanaka M, Omura K, Azuma T, Ohkusa T, Fujimori T, Ono Y, Pauly M, Faber C, Glaesener R, de Goeij AF, Arends JW, Andersen SN, Lovig T, Breivik J, Gaudernack G, Clausen OP, De Angelis PD, Meling GI, Rognum TO, Smith R, Goh HS, Font A, Rosell R, Sun XF, Zhang H, Benhattar J, Losi L, Lee JQ, Wang ST, Clarke PA, Bell S, Quirke P, Bubb VJ, Piris J, Cruickshank NR, Morton D, Fox JC, Al-Mulla F, Lees N, Hall CN, Snary D, Wilkinson K, Dillon D, Costa J, Pricolo VE, Finkelstein SD, Thebo JS, Senagore AJ, Halter SA, Wadler S, Malik S, Krtolica K, Urosevic N: Kirsten ras mutations in patients with colorectal cancer: the 'RASCAL II' study. Br J Cancer. 2001, 85: 692-696. 10.1054/bjoc.2001.1964.CrossRefPubMedPubMedCentral Andreyev HJ, Norman AR, Cunningham D, Oates J, Dix BR, Iacopetta BJ, Young J, Walsh T, Ward R, Hawkins N, Beranek M, Jandik P, Benamouzig R, Jullian E, Laurent-Puig P, Olschwang S, Muller O, Hoffmann I, Rabes HM, Zietz C, Troungos C, Valavanis C, Yuen ST, Ho JW, Croke CT, O'Donoghue DP, Giaretti W, Rapallo A, Russo A, Bazan V, Tanaka M, Omura K, Azuma T, Ohkusa T, Fujimori T, Ono Y, Pauly M, Faber C, Glaesener R, de Goeij AF, Arends JW, Andersen SN, Lovig T, Breivik J, Gaudernack G, Clausen OP, De Angelis PD, Meling GI, Rognum TO, Smith R, Goh HS, Font A, Rosell R, Sun XF, Zhang H, Benhattar J, Losi L, Lee JQ, Wang ST, Clarke PA, Bell S, Quirke P, Bubb VJ, Piris J, Cruickshank NR, Morton D, Fox JC, Al-Mulla F, Lees N, Hall CN, Snary D, Wilkinson K, Dillon D, Costa J, Pricolo VE, Finkelstein SD, Thebo JS, Senagore AJ, Halter SA, Wadler S, Malik S, Krtolica K, Urosevic N: Kirsten ras mutations in patients with colorectal cancer: the 'RASCAL II' study. Br J Cancer. 2001, 85: 692-696. 10.1054/bjoc.2001.1964.CrossRefPubMedPubMedCentral

go back to reference Coleman ML, Marshall CJ, Olson MF: RAS and RHO GTPases in G1-phase cell-cycle regulation. Nat Rev Mol Cell Biol. 2004, 5: 355-366. 10.1038/nrm1365.CrossRefPubMed Coleman ML, Marshall CJ, Olson MF: RAS and RHO GTPases in G1-phase cell-cycle regulation. Nat Rev Mol Cell Biol. 2004, 5: 355-366. 10.1038/nrm1365.CrossRefPubMed

go back to reference Massague J: G1 cell-cycle control and cancer. Nature. 2004, 432: 298-306. 10.1038/nature03094.CrossRefPubMed Massague J: G1 cell-cycle control and cancer. Nature. 2004, 432: 298-306. 10.1038/nature03094.CrossRefPubMed

go back to reference Malumbres M, Barbacid M: RAS oncogenes: the first 30 years. Nat Rev Cancer. 2003, 3: 459-465. 10.1038/nrc1097.CrossRefPubMed Malumbres M, Barbacid M: RAS oncogenes: the first 30 years. Nat Rev Cancer. 2003, 3: 459-465. 10.1038/nrc1097.CrossRefPubMed

go back to reference Pearson G, Robinson F, Beers Gibson T, Xu BE, Karandikar M, Berman K, Cobb MH: Mitogen-activated protein (MAP) kinase pathways: regulation and physiological functions. Endocr Rev. 2001, 22: 153-183. 10.1210/er.22.2.153.PubMed Pearson G, Robinson F, Beers Gibson T, Xu BE, Karandikar M, Berman K, Cobb MH: Mitogen-activated protein (MAP) kinase pathways: regulation and physiological functions. Endocr Rev. 2001, 22: 153-183. 10.1210/er.22.2.153.PubMed

go back to reference Davies H, Bignell GR, Cox C, Stephens P, Edkins S, Clegg S, Teague J, Woffendin H, Garnett MJ, Bottomley W, Davis N, Dicks E, Ewing R, Floyd Y, Gray K, Hall S, Hawes R, Hughes J, Kosmidou V, Menzies A, Mould C, Parker A, Stevens C, Watt S, Hooper S, Wilson R, Jayatilake H, Gusterson BA, Cooper C, Shipley J, Hargrave D, Pritchard-Jones K, Maitland N, Chenevix-Trench G, Riggins GJ, Bigner DD, Palmieri G, Cossu A, Flanagan A, Nicholson A, Ho JW, Leung SY, Yuen ST, Weber BL, Seigler HF, Darrow TL, Paterson H, Marais R, Marshall CJ, Wooster R, Stratton MR, Futreal PA: Mutations of the BRAF gene in human cancer. Nature. 2002, 417: 949-954. 10.1038/nature00766.CrossRefPubMed Davies H, Bignell GR, Cox C, Stephens P, Edkins S, Clegg S, Teague J, Woffendin H, Garnett MJ, Bottomley W, Davis N, Dicks E, Ewing R, Floyd Y, Gray K, Hall S, Hawes R, Hughes J, Kosmidou V, Menzies A, Mould C, Parker A, Stevens C, Watt S, Hooper S, Wilson R, Jayatilake H, Gusterson BA, Cooper C, Shipley J, Hargrave D, Pritchard-Jones K, Maitland N, Chenevix-Trench G, Riggins GJ, Bigner DD, Palmieri G, Cossu A, Flanagan A, Nicholson A, Ho JW, Leung SY, Yuen ST, Weber BL, Seigler HF, Darrow TL, Paterson H, Marais R, Marshall CJ, Wooster R, Stratton MR, Futreal PA: Mutations of the BRAF gene in human cancer. Nature. 2002, 417: 949-954. 10.1038/nature00766.CrossRefPubMed

go back to reference Cowley S, Paterson H, Kemp P, Marshall CJ: Activation of MAP kinase kinase is necessary and sufficient for PC12 differentiation and for transformation of NIH 3T3 cells. Cell. 1994, 77: 841-852. 10.1016/0092-8674(94)90133-3.CrossRefPubMed Cowley S, Paterson H, Kemp P, Marshall CJ: Activation of MAP kinase kinase is necessary and sufficient for PC12 differentiation and for transformation of NIH 3T3 cells. Cell. 1994, 77: 841-852. 10.1016/0092-8674(94)90133-3.CrossRefPubMed

go back to reference Mansour SJ, Matten WT, Hermann AS, Candia JM, Rong S, Fukasawa K, Woude Vande GF, Ahn NG: Transformation of mammalian cells by constitutively active MAP kinase kinase. Science. 1994, 265: 966-970. 10.1126/science.8052857.CrossRefPubMed Mansour SJ, Matten WT, Hermann AS, Candia JM, Rong S, Fukasawa K, Woude Vande GF, Ahn NG: Transformation of mammalian cells by constitutively active MAP kinase kinase. Science. 1994, 265: 966-970. 10.1126/science.8052857.CrossRefPubMed

go back to reference Montesano R, Soriano JV, Hosseini G, Pepper MS, Schramek H: Constitutively active mitogen-activated protein kinase kinase MEK1 disrupts morphogenesis and induces an invasive phenotype in Madin-Darby canine kidney epithelial cells. Cell Growth Differ. 1999, 10: 317-332.PubMed Montesano R, Soriano JV, Hosseini G, Pepper MS, Schramek H: Constitutively active mitogen-activated protein kinase kinase MEK1 disrupts morphogenesis and induces an invasive phenotype in Madin-Darby canine kidney epithelial cells. Cell Growth Differ. 1999, 10: 317-332.PubMed

go back to reference Pinkas J, Leder P: MEK1 signaling mediates transformation and metastasis of EpH4 mammary epithelial cells independent of an epithelial to mesenchymal transition. Cancer Res. 2002, 62: 4781-4790.PubMed Pinkas J, Leder P: MEK1 signaling mediates transformation and metastasis of EpH4 mammary epithelial cells independent of an epithelial to mesenchymal transition. Cancer Res. 2002, 62: 4781-4790.PubMed

go back to reference Schramek H, Feifel E, Healy E, Pollack V: Constitutively active mutant of the mitogen-activated protein kinase kinase MEK1 induces epithelial dedifferentiation and growth inhibition in madin-darby canine kidney-C7 cells. J Biol Chem. 1997, 272: 11426-11433. 10.1074/jbc.272.17.11426.CrossRefPubMed Schramek H, Feifel E, Healy E, Pollack V: Constitutively active mutant of the mitogen-activated protein kinase kinase MEK1 induces epithelial dedifferentiation and growth inhibition in madin-darby canine kidney-C7 cells. J Biol Chem. 1997, 272: 11426-11433. 10.1074/jbc.272.17.11426.CrossRefPubMed

go back to reference Hobbs RM, Silva-Vargas V, Groves R, Watt FM: Expression of activated MEK1 in differentiating epidermal cells is sufficient to generate hyperproliferative and inflammatory skin lesions. J Invest Dermatol. 2004, 123: 503-515. 10.1111/j.0022-202X.2004.23225.x.CrossRefPubMed Hobbs RM, Silva-Vargas V, Groves R, Watt FM: Expression of activated MEK1 in differentiating epidermal cells is sufficient to generate hyperproliferative and inflammatory skin lesions. J Invest Dermatol. 2004, 123: 503-515. 10.1111/j.0022-202X.2004.23225.x.CrossRefPubMed

go back to reference Scholl FA, Dumesic PA, Khavari PA: Mek1 alters epidermal growth and differentiation. Cancer Res. 2004, 64: 6035-6040. 10.1158/0008-5472.CAN-04-0017.CrossRefPubMed Scholl FA, Dumesic PA, Khavari PA: Mek1 alters epidermal growth and differentiation. Cancer Res. 2004, 64: 6035-6040. 10.1158/0008-5472.CAN-04-0017.CrossRefPubMed

go back to reference Dudley DT, Pang L, Decker SJ, Bridges AJ, Saltiel AR: A synthetic inhibitor of the mitogen-activated protein kinase cascade. Proc Natl Acad Sci USA. 1995, 92: 7686-7689. 10.1073/pnas.92.17.7686.CrossRefPubMedPubMedCentral Dudley DT, Pang L, Decker SJ, Bridges AJ, Saltiel AR: A synthetic inhibitor of the mitogen-activated protein kinase cascade. Proc Natl Acad Sci USA. 1995, 92: 7686-7689. 10.1073/pnas.92.17.7686.CrossRefPubMedPubMedCentral

go back to reference Hoshino R, Tanimura S, Watanabe K, Kataoka T, Kohno M: Blockade of the extracellular signal-regulated kinase pathway induces marked G1 cell cycle arrest and apoptosis in tumor cells in which the pathway is constitutively activated: up-regulation of p27(Kip1). J Biol Chem. 2001, 276: 2686-2692. 10.1074/jbc.M006132200.CrossRefPubMed Hoshino R, Tanimura S, Watanabe K, Kataoka T, Kohno M: Blockade of the extracellular signal-regulated kinase pathway induces marked G1 cell cycle arrest and apoptosis in tumor cells in which the pathway is constitutively activated: up-regulation of p27(Kip1). J Biol Chem. 2001, 276: 2686-2692. 10.1074/jbc.M006132200.CrossRefPubMed

go back to reference Collisson EA, De A, Suzuki H, Gambhir SS, Kolodney MS: Treatment of metastatic melanoma with an orally available inhibitor of the Ras-Raf-MAPK cascade. Cancer Res. 2003, 63: 5669-5673.PubMed Collisson EA, De A, Suzuki H, Gambhir SS, Kolodney MS: Treatment of metastatic melanoma with an orally available inhibitor of the Ras-Raf-MAPK cascade. Cancer Res. 2003, 63: 5669-5673.PubMed

go back to reference Sebolt-Leopold JS, Dudley DT, Herrera R, Van Becelaere K, Wiland A, Gowan RC, Tecle H, Barrett SD, Bridges A, Przybranowski S, Leopold WR, Saltiel AR: Blockade of the MAP kinase pathway suppresses growth of colon tumors in vivo. Nat Med. 1999, 5: 810-816. 10.1038/10533.CrossRefPubMed Sebolt-Leopold JS, Dudley DT, Herrera R, Van Becelaere K, Wiland A, Gowan RC, Tecle H, Barrett SD, Bridges A, Przybranowski S, Leopold WR, Saltiel AR: Blockade of the MAP kinase pathway suppresses growth of colon tumors in vivo. Nat Med. 1999, 5: 810-816. 10.1038/10533.CrossRefPubMed

go back to reference Sebolt-Leopold JS, Herrera R: Targeting the mitogen-activated protein kinase cascade to treat cancer. Nat Rev Cancer. 2004, 4: 937-947. 10.1038/nrc1503.CrossRefPubMed Sebolt-Leopold JS, Herrera R: Targeting the mitogen-activated protein kinase cascade to treat cancer. Nat Rev Cancer. 2004, 4: 937-947. 10.1038/nrc1503.CrossRefPubMed

go back to reference Eblen ST, Slack JK, Weber MJ, Catling AD: Rac-PAK signaling stimulates extracellular signal-regulated kinase (ERK) activation by regulating formation of MEK1-ERK complexes. Mol Cell Biol. 2002, 22: 6023-6033. 10.1128/MCB.22.17.6023-6033.2002.CrossRefPubMedPubMedCentral Eblen ST, Slack JK, Weber MJ, Catling AD: Rac-PAK signaling stimulates extracellular signal-regulated kinase (ERK) activation by regulating formation of MEK1-ERK complexes. Mol Cell Biol. 2002, 22: 6023-6033. 10.1128/MCB.22.17.6023-6033.2002.CrossRefPubMedPubMedCentral

go back to reference Wu X, Noh SJ, Zhou G, Dixon JE, Guan KL: Selective activation of MEK1 but not MEK2 by A-Raf from epidermal growth factor-stimulated Hela Cells. J Biol Chem. 1996, 271: 3265-3271. 10.1074/jbc.271.6.3265.CrossRefPubMed Wu X, Noh SJ, Zhou G, Dixon JE, Guan KL: Selective activation of MEK1 but not MEK2 by A-Raf from epidermal growth factor-stimulated Hela Cells. J Biol Chem. 1996, 271: 3265-3271. 10.1074/jbc.271.6.3265.CrossRefPubMed

go back to reference Xu S, Khoo S, Dang A, Witt S, Do V, Zhen E, Schaefer EM, Cobb MH: Differential regulation of mitogen-activated protein/ERK kinase (MEK)1 and MEK2 and activation by a Ras-independent mechanism. Mol Endocrinol. 1997, 11: 1618-1625. 10.1210/me.11.11.1618.CrossRefPubMed Xu S, Khoo S, Dang A, Witt S, Do V, Zhen E, Schaefer EM, Cobb MH: Differential regulation of mitogen-activated protein/ERK kinase (MEK)1 and MEK2 and activation by a Ras-independent mechanism. Mol Endocrinol. 1997, 11: 1618-1625. 10.1210/me.11.11.1618.CrossRefPubMed

go back to reference Liu X, Yan S, Zhou T, Terada Y, Erikson RL: The MAP kinase pathway is required for entry into mitosis and cell survival. Oncogene. 2004, 23: 763-776. 10.1038/sj.onc.1207188.CrossRefPubMed Liu X, Yan S, Zhou T, Terada Y, Erikson RL: The MAP kinase pathway is required for entry into mitosis and cell survival. Oncogene. 2004, 23: 763-776. 10.1038/sj.onc.1207188.CrossRefPubMed

go back to reference Fang JY, Richardson BC: The MAPK signalling pathways and colorectal cancer. Lancet Oncol. 2005, 6: 322-327. 10.1016/S1470-2045(05)70168-6.CrossRefPubMed Fang JY, Richardson BC: The MAPK signalling pathways and colorectal cancer. Lancet Oncol. 2005, 6: 322-327. 10.1016/S1470-2045(05)70168-6.CrossRefPubMed

go back to reference Quaroni A, Wands J, Trelstad RL, Isselbacher KJ: Epithelioid cell cultures from rat small intestine: Characterization by morphologic and immunologic criteria. J Cell Biol. 1979, 80: 248-265. 10.1083/jcb.80.2.248.CrossRefPubMed Quaroni A, Wands J, Trelstad RL, Isselbacher KJ: Epithelioid cell cultures from rat small intestine: Characterization by morphologic and immunologic criteria. J Cell Biol. 1979, 80: 248-265. 10.1083/jcb.80.2.248.CrossRefPubMed

go back to reference Brattain MG, Marks ME, McCombs J, Finely W, Brattain DE: Characterization of human colon carcinoma cell lines isolated from a single primary tumour. Br J Cancer. 1983, 47: 373-381.CrossRefPubMedPubMedCentral Brattain MG, Marks ME, McCombs J, Finely W, Brattain DE: Characterization of human colon carcinoma cell lines isolated from a single primary tumour. Br J Cancer. 1983, 47: 373-381.CrossRefPubMedPubMedCentral

go back to reference Fogh J, Fogh JM, Orfeo T: One hundred and twenty-seven cultured human tumor cell lines producing tumors in nude mice. J Natl Cancer Inst. 1977, 59: 221-226.PubMed Fogh J, Fogh JM, Orfeo T: One hundred and twenty-seven cultured human tumor cell lines producing tumors in nude mice. J Natl Cancer Inst. 1977, 59: 221-226.PubMed

go back to reference Leibovitz A, Stinson JC, McCombs WB, McCoy CE, Mazur KC, Mabry ND: Classification of human colorectal adenocarcinoma cell lines. Cancer Res. 1976, 36: 4562-4569.PubMed Leibovitz A, Stinson JC, McCombs WB, McCoy CE, Mazur KC, Mabry ND: Classification of human colorectal adenocarcinoma cell lines. Cancer Res. 1976, 36: 4562-4569.PubMed

go back to reference Cailleau R, Young R, Olive M, Reeves WJ: Breast tumor cell lines from pleural effusions. J Natl Cancer Inst. 1974, 53: 661-674.PubMed Cailleau R, Young R, Olive M, Reeves WJ: Breast tumor cell lines from pleural effusions. J Natl Cancer Inst. 1974, 53: 661-674.PubMed

go back to reference Rodier G, Makris C, Coulombe P, Scime A, Nakayama K, Nakayama KI, Meloche S: p107 inhibits G1 to S phase progression by down-regulating expression of the F-box protein Skp2. J Cell Biol. 2005, 168: 55-66. 10.1083/jcb.200404146.CrossRefPubMedPubMedCentral Rodier G, Makris C, Coulombe P, Scime A, Nakayama K, Nakayama KI, Meloche S: p107 inhibits G1 to S phase progression by down-regulating expression of the F-box protein Skp2. J Cell Biol. 2005, 168: 55-66. 10.1083/jcb.200404146.CrossRefPubMedPubMedCentral

go back to reference Gopalbhai K, Jansen G, Beauregard G, Whiteway M, Dumas F, Wu C, Meloche S: Negative regulation of MAPKK by phosphorylation of a conserved serine residue equivalent to Ser212 of MEK1. J Biol Chem. 2003, 278: 8118-8125. 10.1074/jbc.M211870200.CrossRefPubMed Gopalbhai K, Jansen G, Beauregard G, Whiteway M, Dumas F, Wu C, Meloche S: Negative regulation of MAPKK by phosphorylation of a conserved serine residue equivalent to Ser212 of MEK1. J Biol Chem. 2003, 278: 8118-8125. 10.1074/jbc.M211870200.CrossRefPubMed

go back to reference Servant MJ, Coulombe P, Turgeon B, Meloche S: Differential regulation of p27(Kip1) expression by mitogenic and hypertrophic factors: Involvement of transcriptional and posttranscriptional mechanisms. J Cell Biol. 2000, 148: 543-556. 10.1083/jcb.148.3.543.CrossRefPubMedPubMedCentral Servant MJ, Coulombe P, Turgeon B, Meloche S: Differential regulation of p27(Kip1) expression by mitogenic and hypertrophic factors: Involvement of transcriptional and posttranscriptional mechanisms. J Cell Biol. 2000, 148: 543-556. 10.1083/jcb.148.3.543.CrossRefPubMedPubMedCentral

go back to reference Gopalbhai K, Meloche S: Repression of mitogen-activated protein kinases ERK1/ERK2 activity by a protein tyrosine phosphatase in rat fibroblasts transformed by upstream oncoproteins. J Cell Physiol. 1998, 174: 35-47. 10.1002/(SICI)1097-4652(199801)174:1<35::AID-JCP5>3.0.CO;2-H.CrossRefPubMed Gopalbhai K, Meloche S: Repression of mitogen-activated protein kinases ERK1/ERK2 activity by a protein tyrosine phosphatase in rat fibroblasts transformed by upstream oncoproteins. J Cell Physiol. 1998, 174: 35-47. 10.1002/(SICI)1097-4652(199801)174:1<35::AID-JCP5>3.0.CO;2-H.CrossRefPubMed

go back to reference Julien C, Coulombe P, Meloche S: Nuclear export of ERK3 by a CRM1-dependent mechanism regulates its inhibitory action on cell cycle progression. J Biol Chem. 2003, 278: 42615-42624. 10.1074/jbc.M302724200.CrossRefPubMed Julien C, Coulombe P, Meloche S: Nuclear export of ERK3 by a CRM1-dependent mechanism regulates its inhibitory action on cell cycle progression. J Biol Chem. 2003, 278: 42615-42624. 10.1074/jbc.M302724200.CrossRefPubMed

go back to reference Macphearson I, Montagnier L: Agar suspension culture for the selective assay of cells transformed by polyoma virus. Virology. 1964, 23: 291-10.1016/0042-6822(64)90301-0.CrossRef Macphearson I, Montagnier L: Agar suspension culture for the selective assay of cells transformed by polyoma virus. Virology. 1964, 23: 291-10.1016/0042-6822(64)90301-0.CrossRef

go back to reference Smyth GK: Linear models and empirical bayes methods for assessing differential expression in microarray experiments. Stat Appl Genet Mol Biol. 2004, 3: Article 3- Smyth GK: Linear models and empirical bayes methods for assessing differential expression in microarray experiments. Stat Appl Genet Mol Biol. 2004, 3: Article 3-

go back to reference Thiery JP: Epithelial-mesenchymal transitions in tumour progression. Nat Rev Cancer. 2002, 2: 442-454. 10.1038/nrc822.CrossRefPubMed Thiery JP: Epithelial-mesenchymal transitions in tumour progression. Nat Rev Cancer. 2002, 2: 442-454. 10.1038/nrc822.CrossRefPubMed

go back to reference Grunert S, Jechlinger M, Beug H: Diverse cellular and molecular mechanisms contribute to epithelial plasticity and metastasis. Nat Rev Mol Cell Biol. 2003, 4: 657-665. 10.1038/nrm1175.CrossRefPubMed Grunert S, Jechlinger M, Beug H: Diverse cellular and molecular mechanisms contribute to epithelial plasticity and metastasis. Nat Rev Mol Cell Biol. 2003, 4: 657-665. 10.1038/nrm1175.CrossRefPubMed

go back to reference Morikawa K, Walker SM, Nakajima M, Pathak S, Jessup JM, Fidler IJ: Influence of organ environment on the growth, selection, and metastasis of human colon carcinoma cells in nude mice. Cancer Res. 1988, 48: 6863-6871.PubMed Morikawa K, Walker SM, Nakajima M, Pathak S, Jessup JM, Fidler IJ: Influence of organ environment on the growth, selection, and metastasis of human colon carcinoma cells in nude mice. Cancer Res. 1988, 48: 6863-6871.PubMed

go back to reference Reddy KB, Nabha SM, Atanaskova N: Role of MAP kinase in tumor progression and invasion. Cancer Metastasis Rev. 2003, 22: 395-403. 10.1023/A:1023781114568.CrossRefPubMed Reddy KB, Nabha SM, Atanaskova N: Role of MAP kinase in tumor progression and invasion. Cancer Metastasis Rev. 2003, 22: 395-403. 10.1023/A:1023781114568.CrossRefPubMed

go back to reference Blasi F, Carmeliet P: uPAR: a versatile signalling orchestrator. Nat Rev Mol Cell Biol. 2002, 3: 932-943. 10.1038/nrm977.CrossRefPubMed Blasi F, Carmeliet P: uPAR: a versatile signalling orchestrator. Nat Rev Mol Cell Biol. 2002, 3: 932-943. 10.1038/nrm977.CrossRefPubMed

go back to reference Fingleton B: Matrix metalloproteinases: roles in cancer and metastasis. Front Biosci. 2006, 11: 479-491. 10.2741/1811.CrossRefPubMed Fingleton B: Matrix metalloproteinases: roles in cancer and metastasis. Front Biosci. 2006, 11: 479-491. 10.2741/1811.CrossRefPubMed

go back to reference Komatsu K, Buchanan FG, Otaka M, Jin M, Odashima M, Horikawa Y, Watanabe S, Dubois RN: Gene expression profiling following constitutive activation of MEK1 and transformation of rat intestinal epithelial cells. Mol Cancer. 2006, 5: 63-10.1186/1476-4598-5-63.CrossRefPubMedPubMedCentral Komatsu K, Buchanan FG, Otaka M, Jin M, Odashima M, Horikawa Y, Watanabe S, Dubois RN: Gene expression profiling following constitutive activation of MEK1 and transformation of rat intestinal epithelial cells. Mol Cancer. 2006, 5: 63-10.1186/1476-4598-5-63.CrossRefPubMedPubMedCentral

go back to reference Reed JC: Mechanisms of apoptosis avoidance in cancer. Curr Opin Oncol. 1999, 11: 68-75. 10.1097/00001622-199901000-00014.CrossRefPubMed Reed JC: Mechanisms of apoptosis avoidance in cancer. Curr Opin Oncol. 1999, 11: 68-75. 10.1097/00001622-199901000-00014.CrossRefPubMed

go back to reference Leu CM, Chang C, Hu C: Epidermal growth factor (EGF) suppresses staurosporine-induced apoptosis by inducing mcl-1 via the mitogen-activated protein kinase pathway. Oncogene. 2000, 19: 1665-1675. 10.1038/sj.onc.1203452.CrossRefPubMed Leu CM, Chang C, Hu C: Epidermal growth factor (EGF) suppresses staurosporine-induced apoptosis by inducing mcl-1 via the mitogen-activated protein kinase pathway. Oncogene. 2000, 19: 1665-1675. 10.1038/sj.onc.1203452.CrossRefPubMed

go back to reference Liu YZ, Boxer LM, Latchman DS: Activation of the Bcl-2 promoter by nerve growth factor is mediated by the p42/p44 MAPK cascade. Nucleic Acids Res. 1999, 27: 2086-2090. 10.1093/nar/27.10.2086.CrossRefPubMedPubMedCentral Liu YZ, Boxer LM, Latchman DS: Activation of the Bcl-2 promoter by nerve growth factor is mediated by the p42/p44 MAPK cascade. Nucleic Acids Res. 1999, 27: 2086-2090. 10.1093/nar/27.10.2086.CrossRefPubMedPubMedCentral

go back to reference Luciano F, Jacquel A, Colosetti P, Herrant M, Cagnol S, Pages G, Auberger P: Phosphorylation of Bim-EL by Erk1/2 on serine 69 promotes its degradation via the proteasome pathway and regulates its proapoptotic function. Oncogene. 2003, 22: 6785-6793. 10.1038/sj.onc.1206792.CrossRefPubMed Luciano F, Jacquel A, Colosetti P, Herrant M, Cagnol S, Pages G, Auberger P: Phosphorylation of Bim-EL by Erk1/2 on serine 69 promotes its degradation via the proteasome pathway and regulates its proapoptotic function. Oncogene. 2003, 22: 6785-6793. 10.1038/sj.onc.1206792.CrossRefPubMed

go back to reference Reginato MJ, Mills KR, Paulus JK, Lynch DK, Sgroi DC, Debnath J, Muthuswamy SK, Brugge JS: Integrins and EGFR coordinately regulate the pro-apoptotic protein Bim to prevent anoikis. Nat Cell Biol. 2003, 5: 733-740. 10.1038/ncb1026.CrossRefPubMed Reginato MJ, Mills KR, Paulus JK, Lynch DK, Sgroi DC, Debnath J, Muthuswamy SK, Brugge JS: Integrins and EGFR coordinately regulate the pro-apoptotic protein Bim to prevent anoikis. Nat Cell Biol. 2003, 5: 733-740. 10.1038/ncb1026.CrossRefPubMed

go back to reference Meloche S, Pouyssegur J: The ERK1/2 mitogen-activated protein kinase pathway as a master regulator of the G1- to S-phase transition. Oncogene. 2007, 26: 3227-3239. 10.1038/sj.onc.1210414.CrossRefPubMed Meloche S, Pouyssegur J: The ERK1/2 mitogen-activated protein kinase pathway as a master regulator of the G1- to S-phase transition. Oncogene. 2007, 26: 3227-3239. 10.1038/sj.onc.1210414.CrossRefPubMed

go back to reference Chang F, Steelman LS, Shelton JG, Lee JT, Navolanic PM, Blalock WL, Franklin R, McCubrey JA: Regulation of cell cycle progression and apoptosis by the Ras/Raf/MEK/ERK pathway (Review). Int J Oncol. 2003, 22: 469-480.PubMed Chang F, Steelman LS, Shelton JG, Lee JT, Navolanic PM, Blalock WL, Franklin R, McCubrey JA: Regulation of cell cycle progression and apoptosis by the Ras/Raf/MEK/ERK pathway (Review). Int J Oncol. 2003, 22: 469-480.PubMed

go back to reference Salomon DS, Brandt R, Ciardiello F, Normanno N: Epidermal growth factor-related peptides and their receptors in human malignancies. Crit Rev Oncol Hematol. 1995, 19: 183-232. 10.1016/1040-8428(94)00144-I.CrossRefPubMed Salomon DS, Brandt R, Ciardiello F, Normanno N: Epidermal growth factor-related peptides and their receptors in human malignancies. Crit Rev Oncol Hematol. 1995, 19: 183-232. 10.1016/1040-8428(94)00144-I.CrossRefPubMed

go back to reference Jonker DJ, O'Callaghan CJ, Karapetis CS, Zalcberg JR, Tu D, Au HJ, Berry SR, Krahn M, Price T, Simes RJ, Tebbutt NC, van Hazel G, Wierzbicki R, Langer C, Moore MJ: Cetuximab for the treatment of colorectal cancer. N Engl J Med. 2007, 357: 2040-2048. 10.1056/NEJMoa071834.CrossRefPubMed Jonker DJ, O'Callaghan CJ, Karapetis CS, Zalcberg JR, Tu D, Au HJ, Berry SR, Krahn M, Price T, Simes RJ, Tebbutt NC, van Hazel G, Wierzbicki R, Langer C, Moore MJ: Cetuximab for the treatment of colorectal cancer. N Engl J Med. 2007, 357: 2040-2048. 10.1056/NEJMoa071834.CrossRefPubMed

go back to reference Boucher MJ, Jean D, Vezina A, Rivard N: Dual role of MEK/ERK signaling in senescence and transformation of intestinal epithelial cells. Am J Physiol Gastrointest Liver Physiol. 2004, 286: G736-746. 10.1152/ajpgi.00453.2003.CrossRefPubMed Boucher MJ, Jean D, Vezina A, Rivard N: Dual role of MEK/ERK signaling in senescence and transformation of intestinal epithelial cells. Am J Physiol Gastrointest Liver Physiol. 2004, 286: G736-746. 10.1152/ajpgi.00453.2003.CrossRefPubMed

go back to reference Komatsu K, Buchanan FG, Katkuri S, Morrow JD, Inoue H, Otaka M, Watanabe S, DuBois RN: Oncogenic potential of MEK1 in rat intestinal epithelial cells is mediated via cyclooxygenase-2. Gastroenterology. 2005, 129: 577-590.CrossRefPubMed Komatsu K, Buchanan FG, Katkuri S, Morrow JD, Inoue H, Otaka M, Watanabe S, DuBois RN: Oncogenic potential of MEK1 in rat intestinal epithelial cells is mediated via cyclooxygenase-2. Gastroenterology. 2005, 129: 577-590.CrossRefPubMed

go back to reference Oldham SM, Clark GJ, Gangarosa LM, Coffey RJ, Der CJ: Activation of the Raf-1/MAP kinase cascade is not sufficient for Ras transformation of RIE-1 epithelial cells. Proc Natl Acad Sci USA. 1996, 93: 6924-6928. 10.1073/pnas.93.14.6924.CrossRefPubMedPubMedCentral Oldham SM, Clark GJ, Gangarosa LM, Coffey RJ, Der CJ: Activation of the Raf-1/MAP kinase cascade is not sufficient for Ras transformation of RIE-1 epithelial cells. Proc Natl Acad Sci USA. 1996, 93: 6924-6928. 10.1073/pnas.93.14.6924.CrossRefPubMedPubMedCentral

go back to reference Chambers AF, Groom AC, MacDonald IC: Dissemination and growth of cancer cells in metastatic sites. Nat Rev Cancer. 2002, 2: 563-572. 10.1038/nrc865.CrossRefPubMed Chambers AF, Groom AC, MacDonald IC: Dissemination and growth of cancer cells in metastatic sites. Nat Rev Cancer. 2002, 2: 563-572. 10.1038/nrc865.CrossRefPubMed

go back to reference Smakman N, Borel Rinkes IH, Voest EE, Kranenburg O: Control of colorectal metastasis formation by K-Ras. Biochim Biophys Acta. 2005, 1756: 103-114.PubMed Smakman N, Borel Rinkes IH, Voest EE, Kranenburg O: Control of colorectal metastasis formation by K-Ras. Biochim Biophys Acta. 2005, 1756: 103-114.PubMed

go back to reference Robertson JH, Sarkar S, Yang SY, Seifalian AM, Winslet MC: In vivo models for early development of colorectal liver metastasis. Int J Exp Pathol. 2008, 89: 1-12. 10.1111/j.1365-2613.2008.00605.x.CrossRefPubMedPubMedCentral Robertson JH, Sarkar S, Yang SY, Seifalian AM, Winslet MC: In vivo models for early development of colorectal liver metastasis. Int J Exp Pathol. 2008, 89: 1-12. 10.1111/j.1365-2613.2008.00605.x.CrossRefPubMedPubMedCentral

go back to reference Licato LL, Keku TO, Wurzelmann JI, Murray SC, Woosley JT, Sandler RS, Brenner DA: In vivo activation of mitogen-activated protein kinases in rat intestinal neoplasia. Gastroenterology. 1997, 113: 1589-1598. 10.1053/gast.1997.v113.pm9352861.CrossRefPubMed Licato LL, Keku TO, Wurzelmann JI, Murray SC, Woosley JT, Sandler RS, Brenner DA: In vivo activation of mitogen-activated protein kinases in rat intestinal neoplasia. Gastroenterology. 1997, 113: 1589-1598. 10.1053/gast.1997.v113.pm9352861.CrossRefPubMed