{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T13:24:22Z","timestamp":1770816262100,"version":"3.50.1"},"reference-count":38,"publisher":"American Association for Cancer Research (AACR)","issue":"7","content-domain":{"domain":["aacrjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2008,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The small GTPase Rac1 can stimulate various signaling pathways that contribute to cell transformation. In particular, the activation of the NF\u03baB transcription factor initiates an antiapoptotic response and promotes cell cycle progression through increased cyclin D1 expression. As a potential oncogenic mechanism to up-regulate this pathway, the overexpression of the Rac1b splicing variant was reported in some colorectal tumors. Rac1b exists predominantly in the active GTP-bound state and selectively promotes the pathway leading to NF\u03baB activation. Here, we studied the role of endogenous Rac1b in colorectal cancer cells. We found that depletion of Rac1b by small interfering RNAs inhibited endogenous NF\u03baB activation and reduced cell viability to 50% within 48 hours. This reduction was due to increased apoptosis, although a reduced G1-S progression rate was also observed. These data show, for the first time, that colorectal cells expressing alternative spliced Rac1b also depend on Rac1b signaling to sustain their survival. (Mol Cancer Res 2008;6(7):1178\u201384)<\/jats:p>","DOI":"10.1158\/1541-7786.mcr-08-0008","type":"journal-article","created":{"date-parts":[[2008,7,21]],"date-time":"2008-07-21T18:18:15Z","timestamp":1216664295000},"page":"1178-1184","update-policy":"https:\/\/doi.org\/10.1158\/crossmark_policy","source":"Crossref","is-referenced-by-count":58,"title":["Increased Rac1b Expression Sustains Colorectal Tumor Cell Survival"],"prefix":"10.1158","volume":"6","author":[{"given":"Paulo","family":"Matos","sequence":"first","affiliation":[{"name":"Centre of Human Genetics, National Health Institute \u2018Dr. Ricardo Jorge\u2019, Lisbon, Portugal"}]},{"given":"Peter","family":"Jordan","sequence":"additional","affiliation":[{"name":"Centre of Human Genetics, National Health Institute \u2018Dr. Ricardo Jorge\u2019, Lisbon, Portugal"}]}],"member":"1086","published-online":{"date-parts":[[2008,7,21]]},"reference":[{"key":"2022060704350462600_BIB1","doi-asserted-by":"crossref","unstructured":"Wennerberg K, Der CJ. Rho-family GTPases: it's not only Rac and Rho (and I like it). J Cell Sci\u20082004;117:1301\u201312.","DOI":"10.1242\/jcs.01118"},{"key":"2022060704350462600_BIB2","doi-asserted-by":"crossref","unstructured":"Jaffe AB, Hall A. Rho GTPases: biochemistry and biology. Annu Rev Cell Dev Biol\u20082005;21:247\u201369.","DOI":"10.1146\/annurev.cellbio.21.020604.150721"},{"key":"2022060704350462600_BIB3","doi-asserted-by":"crossref","unstructured":"Perona R, Montaner S, Saniger L, Sanchez-Perez I, Bravo R, Lacal JC. Activation of the nuclear factor-\u03baB by Rho, CDC42, and Rac-1 proteins. Genes Dev\u20081997;11:463\u201375.","DOI":"10.1101\/gad.11.4.463"},{"key":"2022060704350462600_BIB4","doi-asserted-by":"crossref","unstructured":"Joyce D, Bouzahzah B, Fu M, et al. Integration of Rac-dependent regulation of cyclin D1 transcription through a nuclear factor-\u03baB-dependent pathway. J Biol Chem\u20081999;274:25245\u20139.","DOI":"10.1074\/jbc.274.36.25245"},{"key":"2022060704350462600_BIB5","doi-asserted-by":"crossref","unstructured":"Hinz M, Krappmann D, Eichten A, Heder A, Scheidereit C, Strauss M. NF-\u03baB function in growth control: regulation of cyclin D1 expression and G0\/G1-to-S-phase transition. Mol Cell Biol\u20081999;19:2690\u20138.","DOI":"10.1128\/MCB.19.4.2690"},{"key":"2022060704350462600_BIB6","doi-asserted-by":"crossref","unstructured":"Guttridge DC, Albanese C, Reuther JY, Pestell RG, Baldwin AS, Jr. NF-\u03baB controls cell growth and differentiation through transcriptional regulation of cyclin D1. Mol Cell Biol\u20081999;19:5785\u201399.","DOI":"10.1128\/MCB.19.8.5785"},{"key":"2022060704350462600_BIB7","doi-asserted-by":"crossref","unstructured":"Khosravi-Far R, Solski PA, Clark GJ, Kinch MS, Der CJ. Activation of Rac1, RhoA, and mitogen-activated protein kinases is required for Ras transformation. Mol Cell Biol\u20081995;15:6443\u201353.","DOI":"10.1128\/MCB.15.11.6443"},{"key":"2022060704350462600_BIB8","doi-asserted-by":"crossref","unstructured":"Qiu RG, Chen J, Kirn D, McCormick F, Symons M. An essential role for Rac in Ras transformation. Nature\u20081995;374:457\u20139.","DOI":"10.1038\/374457a0"},{"key":"2022060704350462600_BIB9","doi-asserted-by":"crossref","unstructured":"Joneson T, Bar-Sagi D. Suppression of Ras-induced apoptosis by the Rac GTPase. Mol Cell Biol\u20081999;19:5892\u2013901.","DOI":"10.1128\/MCB.19.9.5892"},{"key":"2022060704350462600_BIB10","doi-asserted-by":"crossref","unstructured":"Malliri A, Van Der Kammen RA, Clark K, Van Der Valk M, Michiels F, Collard JG. Mice deficient in the Rac activator Tiam1 are resistant to Ras-induced skin tumours. Nature\u20082002;417:867\u201371.","DOI":"10.1038\/nature00848"},{"key":"2022060704350462600_BIB11","doi-asserted-by":"crossref","unstructured":"Kissil JL, Walmsley MJ, Hanlon L, et al. Requirement for Rac1 in a K-ras induced lung cancer in the mouse. Cancer Res\u20082007;67:8089\u201394.","DOI":"10.1158\/0008-5472.CAN-07-2300"},{"key":"2022060704350462600_BIB12","doi-asserted-by":"crossref","unstructured":"Sahai E, Marshall CJ. Rho-GTPases and cancer. Nat Rev Cancer\u20082002;2:133\u201342.","DOI":"10.1038\/nrc725"},{"key":"2022060704350462600_BIB13","doi-asserted-by":"crossref","unstructured":"Fritz G, Just I, Kaina B. Rho GTPases are overexpressed in human tumours. Int J Cancer\u20081999;81:682\u20137.","DOI":"10.1002\/(SICI)1097-0215(19990531)81:5<682::AID-IJC2>3.0.CO;2-B"},{"key":"2022060704350462600_BIB14","doi-asserted-by":"crossref","unstructured":"Schnelzer A, Prechtel D, Knaus U, et al. Rac1 in human breast cancer: overexpression, mutation analysis, and characterisation of a new isoform, Rac1b. Oncogene\u20082000;19:3013\u201320.","DOI":"10.1038\/sj.onc.1203621"},{"key":"2022060704350462600_BIB15","doi-asserted-by":"crossref","unstructured":"Engers R, Zwaka TP, Gohr L, Weber A, Gerharz CD, Gabbert HE. Tiam1 mutations in human renal-cell carcinomas. Int J Cancer\u20082000;88:369\u201376.","DOI":"10.1002\/1097-0215(20001101)88:3<369::AID-IJC8>3.0.CO;2-K"},{"key":"2022060704350462600_BIB16","doi-asserted-by":"crossref","unstructured":"Rossman KL, Der CJ, Sondek J. GEF means go: turning on RHO GTPases with guanine nucleotide-exchange factors. Nat Rev Mol Cell Biol\u20082005;6:167\u201380.","DOI":"10.1038\/nrm1587"},{"key":"2022060704350462600_BIB17","unstructured":"Gildea JJ, Seraj MJ, Oxford G, et al. RhoGDI2 is an invasion and metastasis suppressor gene in human cancer. Cancer Res\u20082002;62:6418\u201323."},{"key":"2022060704350462600_BIB18","doi-asserted-by":"crossref","unstructured":"Chumbalkar VC, Subhashini C, Dhople VM, et al. Differential protein expression in human gliomas and molecular insights. Proteomics\u20082005;5:1167\u201377.","DOI":"10.1002\/pmic.200401202"},{"key":"2022060704350462600_BIB19","doi-asserted-by":"crossref","unstructured":"Jordan P, Braza\u0303o R, Boavida MG, Gespach C, Chastre E. Cloning of a novel human Rac1b splice variant with increased expression in colorectal tumours. Oncogene\u20081999;18:6835\u20139.","DOI":"10.1038\/sj.onc.1203233"},{"key":"2022060704350462600_BIB20","doi-asserted-by":"crossref","unstructured":"Matos P, Skaug J, Marques B, et al. Small GTPase Rac1: structure, localisation and expression of the human gene. Biochem Biophys Res Commun\u20082000;277:741\u201351.","DOI":"10.1006\/bbrc.2000.3743"},{"key":"2022060704350462600_BIB21","doi-asserted-by":"crossref","unstructured":"Matos P, Collard J, Jordan P. Tumour-related alternative-spliced Rac1b is not regulated by Rho-GDI and exhibits selective downstream signalling. J Biol Chem\u20082003;278:50442\u20138.","DOI":"10.1074\/jbc.M308215200"},{"key":"2022060704350462600_BIB22","doi-asserted-by":"crossref","unstructured":"Fiegen D, Haeusler LC, Blumenstein L, et al. Alternative splicing of Rac1 generates Rac1b, a self-activating GTPase. J Biol Chem\u20082004;279:4743\u20139.","DOI":"10.1074\/jbc.M310281200"},{"key":"2022060704350462600_BIB23","doi-asserted-by":"crossref","unstructured":"Singh A, Karnoub AE, Palmby TR, Lengyel E, Sondek J, Der JC. Rac1b, a tumour associated, constitutively active Rac1 splice variant, promotes cellular transformation. Oncogene\u20082004;23:9369\u201380.","DOI":"10.1038\/sj.onc.1208182"},{"key":"2022060704350462600_BIB24","doi-asserted-by":"crossref","unstructured":"Radisky DC, Levy DD, Littlepage LE, et al. Rac1b and reactive oxygen species mediate MMP-3-induced EMT and genomic instability. Nature\u20082005;436:123\u20137.","DOI":"10.1038\/nature03688"},{"key":"2022060704350462600_BIB25","doi-asserted-by":"crossref","unstructured":"Matos P, Jordan P. Expression of Rac1b stimulates NF-\u03baB-mediated cell survival and G1\/S-progression. Exp Cell Res\u20082005;305:292\u20139.","DOI":"10.1016\/j.yexcr.2004.12.029"},{"key":"2022060704350462600_BIB26","doi-asserted-by":"crossref","unstructured":"Matos P, Jordan P. RAC1, but not RAC1B, stimulates RELB-mediated gene transcription in colorectal cancer cells. J Biol Chem\u20082006;281:13724\u201332.","DOI":"10.1074\/jbc.M513243200"},{"key":"2022060704350462600_BIB27","doi-asserted-by":"crossref","unstructured":"Esufali S, Charames GS, Pethe VV, Buongiorno P, Bapat B. Activation of tumor-specific splice variant Rac1b by dishevelled promotes canonical Wnt signaling and decreased adhesion of colorectal cancer cells. Cancer Res\u20082007;67:2469\u201379.","DOI":"10.1158\/0008-5472.CAN-06-2843"},{"key":"2022060704350462600_BIB28","doi-asserted-by":"crossref","unstructured":"Olson MF, Ashworth A, Hall A. An essential role for Rho, Rac, and Cdc42 GTPases in cell cycle progression through G1. Science\u20081995;269:1270\u20132.","DOI":"10.1126\/science.7652575"},{"key":"2022060704350462600_BIB29","doi-asserted-by":"crossref","unstructured":"Moore KA, Sethi R, Doanes AM, et al. Rac1 is required for cell proliferation and G2\/M progression. Biochem J\u20081997;326:17\u201320.","DOI":"10.1042\/bj3260017"},{"key":"2022060704350462600_BIB30","doi-asserted-by":"crossref","unstructured":"Villalonga P, Ridley AJ. Rho GTPases and cell cycle control. Growth Factors\u20082006;24:159\u201364.","DOI":"10.1080\/08977190600560651"},{"key":"2022060704350462600_BIB31","doi-asserted-by":"crossref","unstructured":"Ruggieri R, Chuang YY, Symons M. The small GTPase Rac suppresses apoptosis caused by serum deprivation in fibroblasts. Mol Med\u20082001;7:293\u2013300.","DOI":"10.1007\/BF03402212"},{"key":"2022060704350462600_BIB32","doi-asserted-by":"crossref","unstructured":"Pervaiz S, Cao J, Chao OS, Chin YY, Cle\u0301ment MV. Activation of the Rac GTPase inhibits apoptosis in human tumor cells. Oncogene\u20082001;20:6263\u20138.","DOI":"10.1038\/sj.onc.1204840"},{"key":"2022060704350462600_BIB33","doi-asserted-by":"crossref","unstructured":"Sun SC, Ganchi PA, Ballard DW, Greene WC. NF-\u03baB controls expression of inhibitor I\u03baB\u03b1: evidence for an inducible autoregulatory pathway. Science\u20081993;259:1912\u20135.","DOI":"10.1126\/science.8096091"},{"key":"2022060704350462600_BIB34","doi-asserted-by":"crossref","unstructured":"Brown K, Park S, Kanno T, Franzoso G, Siebenlist U. Mutual regulation of the transcriptional activator NF-\u03baB and its inhibitor, I\u03baB\u03b1. Proc Natl Acad Sci U S A\u20081993;90:2532\u20136.","DOI":"10.1073\/pnas.90.6.2532"},{"key":"2022060704350462600_BIB35","doi-asserted-by":"crossref","unstructured":"Chen LF, Greene WC. Shaping the nuclear action of NF-\u03baB. Nat Rev Mol Cell Biol\u20082004;5:392\u2013401.","DOI":"10.1038\/nrm1368"},{"key":"2022060704350462600_BIB36","doi-asserted-by":"crossref","unstructured":"Jin S, Ray RM, Johnson LR. Rac1 mediates intestinal epithelial cell apoptosis via JNK. Am J Physiol Gastrointest Liver Physiol\u20082006;291:G1137\u201347.","DOI":"10.1152\/ajpgi.00031.2006"},{"key":"2022060704350462600_BIB37","doi-asserted-by":"crossref","unstructured":"Eom YW, Yoo MH, Woo CH, et al. Implication of the small GTPase Rac1 in the apoptosis induced by UV in Rat-2 fibroblasts. Biochem Biophys Res Commun\u20082001;285:825\u20139.","DOI":"10.1006\/bbrc.2001.5233"},{"key":"2022060704350462600_BIB38","doi-asserted-by":"crossref","unstructured":"Ho TC, Yang YC, Cheng HC, et al. Activation of mitogen-activated protein kinases is essential for hydrogen peroxide-induced apoptosis in retinal pigment epithelial cells. Apoptosis\u20082006;11:1899\u2013908.","DOI":"10.1007\/s10495-006-9403-6"}],"container-title":["Molecular Cancer Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/aacrjournals.org\/mcr\/article-pdf\/6\/7\/1178\/3142849\/1178.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/aacrjournals.org\/mcr\/article-pdf\/6\/7\/1178\/3142849\/1178.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,6,7]],"date-time":"2022-06-07T05:49:01Z","timestamp":1654580941000},"score":1,"resource":{"primary":{"URL":"https:\/\/aacrjournals.org\/mcr\/article\/6\/7\/1178\/90388\/Increased-Rac1b-Expression-Sustains-Colorectal"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,7,1]]},"references-count":38,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2008,7,21]]},"published-print":{"date-parts":[[2008,7,1]]}},"URL":"https:\/\/doi.org\/10.1158\/1541-7786.mcr-08-0008","relation":{},"ISSN":["1541-7786","1557-3125"],"issn-type":[{"value":"1541-7786","type":"print"},{"value":"1557-3125","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,7,1]]}}}