Oncogenic Ras and its role in tumor cell invasion and metastasis


Oncogenic Ras and its role in tumor cell invasion and metastasis

112 P.M. Campbell, C.J. Der / Seminars in Cancer Biology 14 (2004) 105–114[38] Downward J. Cell cycle: routine role for Ras. Curr Biol1997;7(4):R258–60.[39] Pruitt K, Der CJ. Ras and Rho regulation of the cell cycle andoncogenesis. Cancer Lett 2001;171(1):1–10.[40] Chong H, Vikis HG, Guan KL. Mechanisms of regulating the Rafkinase family. Cell Signal 2003;15(5):463–9.[41] Davies H, Bignell GR, Cox C, Stephens P, Edkins S, Clegg S,et al. Mutations of the BRAF gene in human cancer. Nature2002;417(6892):949–54.[42] Seth A, Gonzalez FA, Gupta S, Raden DL, Davis RJ. Signal transductionwithin the nucleus by mitogen-activated protein kinase. JBiol Chem 1992;267(34):24796–804.[43] Chambers AF, Tuck AB. Ras-responsive genes and tumor metastasis.Crit Rev Oncog 1993;4(2):95–114.[44] Yordy JS, Muise-Helmericks RC. Signal transduction and the Etsfamily of transcription factors. Oncogene 2000;19(55):6503–13.[45] Webb CP, Van Aelst L, Wigler MH, Vande Woude GF. Signalingpathways in Ras-mediated tumorigenicity and metastasis. PNAS1998;95(15):8773–8.[46] Posada J, Yew N, Ahn NG, Vande Woude GF, Cooper JA. Mosstimulates MAP kinase in Xenopus oocytes and activates a MAPkinase kinase in vitro. Mol Cell Biol 1993;13(4):2546–53.[47] Mansour SJ, Matten WT, Hermann AS, Candia JM, Rong S, FukasawaK, et al. Transformation of mammalian cells by constitutivelyactive MAP kinase kinase. Science 1994;265(5174):966–70.[48] Webb CP, Taylor GA, Jeffers M, Fiscella M, Oskarsson M, ResauJH, et al. Evidence for a role of Met-HGF/SF during Ras-mediatedtumorigenesis/metastasis. Oncogene 1998;17(16):2019–25.[49] Rodriguez-Viciana P, Warne PH, Dhand R, Vanhaesebroeck B, GoutI, Fry MJ, et al. Phosphatidylinositol-3-OH kinase as a direct targetof Ras. Nature 1994;370(6490):527–32.[50] Mayo MW, Wang CY, Cogswell PC, Rogers-Graham KS, LoweSW, Der CJ, et al. Requirement of NF-kappaB activation to suppressp53-independent apoptosis induced by oncogenic Ras. Science1997;278(5344):1812–5.[51] Shaw LM, Rabinovitz I, Wang HH, Toker A, Mercurio AM. Activationof phosphoinositide 3-OH kinase by the alpha6beta4 integrinpromotes carcinoma invasion. Cell 1997;91(7):949–60.[52] Burgering BM, Coffer PJ. Protein kinase B (C-Akt) inphosphatidylinositol-3-OH kinase signal transduction. Nature1995;376(6541):599–602.[53] Shaw LM. ldentiftcation of Insulin Receptor Substrate 1 (IRS-1)and IRS-2 as Signaling Intermediates in the {alpha}6{beta}4Integrin-Dependent Activation of Phosphoinositide 3-OH Kinaseand Promotion of Invasion. Mol Cell Biol 2001;21(15):5082–93.[54] Frisch SM, Ruoslahti E. Integrins and anoikis. Curr Opin Cell Biol1997;9(5):701–6.[55] Khwaja A, Rodriguez-Viciana P, Wennsom S, Warne PH, DownwardJ. Matrix adhesion and Ras transformation both accurate aphosphoinositide 3-CH kinase and protein kinase B/Akt cellularsurvival pathway. Embo J 1997;16(10):2783–93.[56] McFall A, Utku A, Lambett QT, Kusa A, Rogers-Graham K, DerCJ. Oncogenic Ras blocks anoikis by activation of a novel effectorpathway independent of phosphatidylinositol 3-kinase. Mol CellBiol 2001;21(16):5488–99.[57] Nimnual AS, Yatsula BA, Bar-Sagi D. Coupling of Ras and Racguanosine triphosphatases through the Ras exchanger Sos. Science1998;279(5350):)560–3.[58] Han J, Luby-Phelps K, Das B, Shu X, Xia Y, Mosteller RD, etal. Role of substrates and products of PI 3-kinase in regulatingactivation of Rac-related guanosine triphosphatases by Vav. Science1998;279(5350):558–60.[59] Etienne-Manneville S, Hall A. Rho GTPases in cell biology. Nature2002;420(6916):629–35.[60] Schmitz AA, Govek EE, Bottner B, Van Aelst L. Rho GTPases:signaling, migration, and invasion. Exp Cell Res 2000;261(1):1–12.[61] Sahai E, Marshall CJ. RHO-GTPases and cancer. Nat Rev Cancer2002;2(2):133–42.[62] Feig LA. Ral-GTPases: approaching their 15 minutes of fame.Trends Cell Biol 2003;13(8):419–25.[63] Hamad NM, Elconin JH, Karnoub AE, Bai W, Rich JN, AbrahamRT, et al. Distinct requirements for Ras oncogenesis in humanversus mouse cells. Genes Dev 2002;16(16):2045–57.[64] Ward Y, Wang W, Woodhouse E, Linnoila I, Liotta L, Kelly K.Signal pathways which promote invasion and metastasis: criticaland distinct contributions of extracellular signal-regulated kinaseand Ral-specific guanine exchange factor pathways. Mol Cell Biol2001;21(17):5958–69.[65] Gildea JJ, Harding MA, Seraj MJ, Guiding KM, Theodorescu D.The role of Ral A in epidermal growth factor receptor-regulatedcell motility. Cancer Res 2002;62(4):982–5.[66] Lambert JM, Lambert QT, Reuther GW, Malliri A, SiderovskiDP, Sondek J, et al. Tiam1 mediates Ras activation of Rac by aPI(3)K-independent mechanism. Nat Cell Biol 2002;4(8):621–5.[67] Habets GG, Scholtes EH, Zuydgeest D, van der Kammen RA,Stam JC, Berns A, et al. Identification of an invasion-inducinggene, Tiam-1, that encodes a protein with homology to GDP-GTPexchangers for Rho-like proteins. Cell 1994;77(4):537–49.[68] Michiels F, Habets GG, Stam JC, van der Kammen RA, Collard JG.A role for Rac in Tiam1-induced membrane ruffling and invasion.Nature 1995;375(6529):338–40.[69] Malliri A, van der Kammen RA, Clark K, van der Valk M, MichielsF, Collard JG. Mice deficient in the Rac activator Tiam1 are resistantto Ras-induced skin turnouts. Nature 2002;417(6891):867–71.[70] Rubin JS, Bottaro DP, Aaronson SA. Hepatocyte growth factor/scatterfactor and its receptor, the c-met proto-oncogene product.Biochim Biophys Acta 1993;1155(3):357–71.[71] Jeffers M, Rong S, Vande Woude G. Enhanced tumorigenicity andinvasion-metastasis by hepatocyte growth factor/scatter factor-metsignalling in human cells concomitant with induction of the urokinaseproteolysis network. Mol Cell Biol 1996;16(3):1115–25.[72] Furge KA, Kiewlich D, Le P, Vo MN, Faure M, Howlett AR, et al.Suppression of Ras-mediated tumorigenicity and metastasis throughinhibition of the Met receptor tyrosine kinase. Proc Natl Acad SciUSA 2001;98(19):10722–7.[73] Gambarotta G, Boccaccio C, Giordano S, Ando M, Stella MC,Comoglio PM. Ets up-regulates MET transcription. Oncogene1996;13(9):1911–7.[74] Galang CK, Der CJ, Hauser CA. Oncogenic Ras can induce transcriptionalactivation through a variety of promoter elements, includingtandem c-Ets-2 binding sites. Oncogene 1994;9(10):2913–21.[75] Zohn IM, Campbell SL, Khosravi-Far R, Rossman KL, Der CJ. Rhofamily proteins and Ras transformation: the RHOad less traveledgets congested. Oncogene 1998;17(11 Reviews):1415–38.[76] Mertens AE, Roovers RC, Collard JG. Regulation of Tiam1-Racsignalling. FEBS Lett 2003;546(1):11–6.[77] Hall A. Rho GTPases and the actin cytoskeleton. Science1998;279(5350):509–14.[78] Vial E, Sahai E, Marshall CJ. ERK-MAPK signaling coordinatelyregulates activity of Rac1 and RhoA for tumor cell motility. CancerCell 2003;4(1):67–79.[79] Oxford G, Theodorescu D. Ras superfamily monomeric G proteinsin carcinoma cell motility. Cancer Lett 2003;189(2):117–28.[80] Van Aelst L, Symons M. Role of Rho family GTPases in epithelialmorphogenesis. Genes Dev 2002;16(9):1032–54.[81] Hawkins PT, Eguinoa A, Qiu RG, Stokoe D, Cooke FT, WaltersR, et al. PDGF stimulates an increase in GTP-Rac via activationof phosphoinositide 3-kinase. Curr Biol 1995;5(4):393–403.[82] Benard V, Bohl BP, Bokoch GM. Characterization of Rac andCdc42 Activation in Chemoattractant-stimulated Human NeutrophilsUsing a Novel Assay for Active GTPases. J Biol Chem1999;274(19):13198–204.

P.M. Campbell, C.J. Der / Seminars in Cancer Biology 14 (2004) 105–114 113[83] Genot EM, Arrieumerlou C, Ku G, Burgering BMT, Weiss A,Kramer IM. The T-Cell Receptor Regulates Akt (Protein Kinase B)via a Pathway Involving Rac1 and Phosphatidylinositide 3-Kinase.Mol Cell Biol 2000;20(15):5469–78.[84] Weiner OD, Neilsen PO, Prestwich GD, Kirschner MW, CantleyLC, Bourne HR. A PtdInsP(3)- and Rho GTPase-mediated positivefeedback loop regulates neutrophil polarity. Nat Cell Biol2002;4(7):509–13.[85] Cozzolino M, Stagni V, Spinardi L, Campioni N, Fiorentini C, SalvatiE, et al. p120 Catenin Is Required for Growth Factor-dependentCell Motility and Scattering in Epithelial Cells. Mol Biol Cell2003;14(5):1964–77.[86] Hay ED. An overview of epithelio-mesenchymal transformation.Acta Anat (Basel) 1995;154(1):8–20.[87] Shieh DB, Godleski J, Herndon II JE, Azuma T, Mercer H,Sugarbaker DJ, et al. Cell motility as a prognostic factor in StageI nonsmall cell lung carcinoma: the role of gelsolin expression.Cancer 1999;85(1):47–57.[88] Rao J, Seligson D, Visapaa H, Horvath S, Eeva M, Michel K,et al. Tissue microarray analysis of cytoskeletal actin-associatedbiomarkers gelsolin and E-cadherin in urothelial carcinoma. Cancer2002;95(6):1247–57.[89] Azuma T, Witke W, Stossel TP, Hartwig JH, Kwiatkowski DJ.Gelsolin is a downstream effector of rac for fibroblast motility.EMBO J 1998;17(5):1362–70.[90] De Corte V, Bruyneel E, Boucherie C, Mareel M, Vandekerckhove J,Gettemans J. Gelsolin-induced epithelial cell invasion is dependenton Ras-Rac signaling. EMBO J 2002;21(24):6781–90.[91] Oft M, Peli J, Rudaz C, Schwarz H, Beug H, Reichmann E.TGF-beta1 and Ha-Ras collaborate in modulating the phenotypicplasticity and invasiveness of epithelial tumor cells. Genes Dev1996;10(19):2462–77.[92] Oft M, Heider KH, Beug H. TGFbeta signaling is necessaryfor carcinoma cell invasiveness and metastasis. Curr Biol1998;8(23):1243–52.[93] Arsura M, Mercurio F, Oliver AL, Thorgeirsson SS, SonensheinGE. Role of the IkappaB kinase complex in oncogenic Ras- andRaf-mediated transformation of rat liver epithetial cells. Mol CellBiol 2000;20(15):5381–91.[94] Janda E, Lehmann K, Killisch I, Jechlinger M, Herzig M, DownwardJ, et al. Ras and TGF{beta} cooperatively regulate epithelial cellplasticity and metastasis: dissection of Ras signaling pathways. JCell Biol 2002;156(2):299–314.[95] Westermarck J, Kahari VM. Regulation of matrix metalloproteinaseexpression in tumor invasion. Faseb J 1999;13(8):781–92.[96] Bernhard EJ, Gruber SB, Muschel RJ. Direct evidence linkingexpression of matrix metalloproteinase 9 (92-kDa gelatinase/collagenase)to the metastatic phenotype in transformed ratembryo cells. Proc Natl Acad Sci USA 1994;91(10):4293–7.[97] Ballin M, Gomez DE, Sinha CC, Thorgeirsson UP. Ras oncogenemediated induction of a 92 kDa metalloproteinase; strong correlationwith the malignant phenotype. Biochem Biophys Res Commun1988;154(3):832–8.[98] Thorgeirsson UP, Turpeenniemi-Hujanen T, Williams JE, WestinEH, Heilman CA, Talmadge JE, et al. NIH/3T3 cells transfected withhuman tumor DNA containing activated ras oncogenes express themetastatic phenotype in nude mice. Mol Cell Biol 1985;5(1):259–62.[99] Simon C, Goepfert H, Boyd D. Inhibition of the p38 mitogenactivatedprotein kinase by SB 203580 blocks PMA-induced Mr92,000 type IV collagenase secretion and in vitro invasion. CancerRes 1998;58(6):1135–9.[100] Westermarck J, Li S-P, Kallunki T, Han J, Kahari V-M. p38Mitogen-Activated Protein Kinase-Dependent Activation of ProteinPhosphatases 1 and 2A Inhibits MEK1 and MIK2 Activityand Collagenase 1 (MMP-1) Gene Expression. Mol Cell Biol2001;21(7):2373–83.[101] Yang JQ, Zhao W, Duan H, Robbins ME, Buettner GR, OberleyLW, et al. v-Ha-RaS oncogene upregulates the 92-kDa type N collagenase(MMP-9) gene by increasing cellular superoxide productionand activating NF-kappaB. Free Radic Biol Med 2001;31(4):520–9.[102] Gum R, Lengyel E, Juarez J, Chen JH, Sato H, Seiki M, et al.Stimulation of 92-kDa gelatinase B promoter activity by ras ismitogen-activated protein kinase kinase 1-independent and requiresmultiple transcription factor binding sites including closely spacedPEA3/ets and AP-1 sequences. J Biol Chem 1996;271(18):10672–80.[103] Lengye E, Singh B, Gum R, Nerlov C, Sabichi A, Birrer M, et al.Regulation of urokinase-type plasminogen activator expression bythe v-mos oncogene. Oncogene 1995;11(12):2639–48.[104] Muller SM, Okan E, Jones P. Regulation of Urokinase ReceptorTranscription by Ras- and Rho-Family GTPases. Biochemical andBiophysical Research Communications 2000;270(3):892–8.[105] Okan E, Drewett V, Shaw PE, Jones P. The small-GTPase RaIAactivates transcription of the urokinase plasminogen activator receptor(uPAR) gene via an AP1-dependent mechanism. Oncogene2001;20(15):1816–24.[106] Aguirre-Ghiso JA, Frankel P, Farias EF, Lu Z, Jiang H, Olsen A,et al. RaIA requirement for v-Src- and v-Ras-induced tumorigenicityand overproduction of urokinase-type plasminogen activator:involvement of metalloproteases. Oncogene 1999;18(33):4718–25.[107] Takahashi C, Sheng Z, Horan TP, Kitayama H, Maki M, HitomiK, et al. Regulation of matrix metalloproteinase-9 and inhibitionof tumor invasion by the membrane-anchored glycoprotein RECK.PNAS 1998;95(22):13221–6.[108] Chambers AF, Colella R, Denhardt DT, Wilson SM. Increased expressionof cathepsins L and B and decreased activity of their inhibitorsin metastatic, ras-transformed NIH 3T3 cells. Mol Carcinog1992;5(3):238–45.[109] Zhang JY, Schultz RM. Fibroblasts transformed by different rasoncogenes show dissimilar patterns of protease gene expression andregulation. Cancer Res 1992;52(23):6682–9.[110] Premzl A, Zavasnik-Bergant V, Turk V, Kos J. Intracellular andextracellular cathepsin B facilitate invasion of MCF-10A neoT cellsthrough reconstituted extracellular matrix in vitro. Exp Cell Res2003;283(2):206–14.[111] Bervar A, Zajc I, Sever N, Katunuma N, Sloane BF, Lah TT.Invasiveness of transformed human breast epithelial cell lines isrelated to cathepsin B and inhibited by cysteine proteinase inhibitors.Biol Chem 2003;384(3):447–55.[112] Thiery JP. Epithelial-mesenchymal transitions in tumour progression.Nat Rev Cancer 2002;2(6):442–54.[113] Gumbiner BM. Cell adhesion: the molecular basis of tissue architectureand morphogenesis. Cell 1996;84(3):345–57.[114] Takahashi K, Nakanishi H, Miyahara M, Mandai K, Satoh K,Satoh A, et al. Nectin/PRR: an immunoglobulin-like cell adhesionmolecule recruited to cadherin-based adherens junctions throughinteraction with Afadin, a PDZ domain-containing protein. J CellBiol 1999;145(3):539–49.[115] Yan Z, Chen M, Perucho M, Friedman E. Oncogenic Ki-ras but notoncogenic Ha-ras blocks integrin beta1-chain maturation in colonepithelial cell. J Biol Chem 1997;272(49):30928–36.[116] Schlaepfer DD, Hanks SK, Hunter T, van der Geer P. Integrinmediatedsignal transduction linked to Ras pathway by GRB2 bindingto focal adhesion kinase. Nature 1994;372(6508):786–91.[117] Rak J, Misuhashi Y, Bayko L, Filmus J, Shirasawa S, SasazukiT, et al. Mutant ras oncogenes upregulate VEGF/VPF expression:implications for induction and inhibition of tumor angiogenesis.Cancer Res 1995;55(20):4575–80.[118] Grugel S, Finkenzeller G, Weindel K, Barleon B, Marme D. Bothv-Ha-Ras and v-Raf stimulate expression of the vascular endothelialgrowth factor in NIH 3T3 cells. J Biol Chem 1995;270(43):25915–9.

114 P.M. Campbell, C.J. Der / Seminars in Cancer Biology 14 (2004) 105–114[119] Chin L, Tam A, Pomerantz J, Wong M, Holash J, Bardeesy N, etal. Essential role for oncogenic Ras in tumour maintenance. Nature1999;400(6743):468–72.[120] Arbiser JL, Moses MA, Fernandez CA, Ghiso N, Cao Y, KlauberN, et al. Oncogenic H-ras stimulates tumor angiogenesis by twodistinct pathways. PNAS 1997;94(3):861–6.[121] Al-Mulla F, Going JJ, Sowden ET, Winter A, Pickford IR, BirnieGD. Heterogeneity of mutant versus wild-type Ki-ras in primaryand metastatic colorectal carcinomas, and association of codon-12valine with early mortality. J Pathol 1998;185(2):130–8.[122] Andreyev HJ, Norman AR, Cunningham D, Oates JR, Clarke PA.Kirsten ras mutations in patients with colorectal cancer: the multicenter“RASCAL” study. J Natl Cancer Inst 1998;90(9):675–84.[123] Andreyev HJ, Norman AR, Cunningham D, Oates J, Dix BR,Lacopette BJ, et al. Kirsten ras mutations in patients with colorectalcancer: the ‘RASCAL II’ study. Br J Cancer 2001;85(6):692–6.[124] Pasqualini R, Koivunen E, Kain R, Lahdenranta J, Sakamoto M,Stryhn A, et al. Aminopeptidase N is a receptor for tumor-homingpeptides and a target for inhibiting angiogenesis. Cancer Res2000;60(3):722–7.[125] Bhagwat SV, Petrovic N, Okamoto Y, Shapiro LH. The angiogenicregulator CD13/APN is a transcriptional target of Ras signalingpathways in endothelial morphogenesis. Blood 2003;101(5):1818–26.[126] Casanova ML, Larcher F, Casanova B, Murillas R, Fernandez-Acenero MJ, Villanueva C, et al. A cribcal role for ras-rnediited,epidermal growth factor receptor-dependent angiogenesis in mouseskin carcinogenesis. Cancer Res 2002;62(12):3402–7.[127] Li T, Sparano JA. Inhibiting Ras signaling in the therapy of breastcancer. Clin Breast Cancer 2003;3(6):405–16, discussion 417–20.[128] Cohen SJ, Ho L, Ranganathan S, Abbruzzese JL, Alpaugh RK,Beard M, et al. Phase II and pharmacodynamic study of the farnesyltransferaseinhibitor R115777 as initial therapy in patients with mestaticpancreatic adenocarcinoma. J Clin Oncol 2003;21(7):1301–6.[129] Cox AD, Der CJ. Ras family signaling: therapeutic targeting. CancerBiol Ther 2002;1(6):599–606.

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