Differential expression of Rac1 identifies its target genes and its contribution to progression of colorectal cancer.
The small GTPase Rac1 is involved in the regulation of critical cellular functions, such as transcription control, cell cycle, and organization of actin cytoskeleton. Rac1 signalling modulates cancer progression since its overexpression leads to an increased tumour growth of xenografts of human colorectal tumour cells, while a drastic reduction of Rac1 expression by siRNA interferes with cancer progression (Espina et al., unpublished results). We aimed to study the molecular basis for the specific contribution of Rac1 in the progression of colorectal cancer. Comparative microarray analysis of a human colorectal carcinoma cell line genetically engineered to display different levels of Rac1 identified novel target genes for this GTPase. These results suggest that Rac1 plays a critical role in signalling transduction pathways relevant to human colorectal tumour progression, such as activation of Wnt signalling, inhibition of TGF-beta signalling, and enhancement of metastasis-inducing genes.
Gómez del Pulgar
Teresa
T
Translational Oncology Unit CSIC-UAM-La Paz, Centro Nacional de Biotecnología, Madrid, Spain.
Bandrés
Eva
E
Espina
Carolina
C
Valdés-Mora
Fátima
F
Pérez-Palacios
Rosa
R
García-Amigot
Fermín
F
García-Foncillas
Jesús
J
Lacal
Juan Carlos
JC
D048868:Adaptor Proteins, Signal Transducing; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004268:DNA-Binding Proteins / Q000235:genetics; D037483:Galectin 1 / Q000235:genetics; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000235:genetics; D020783:Matrix Metalloproteinase 7 / Q000235:genetics; D008565:Membrane Proteins / Q000378:metabolism; D008840:Microfilament Proteins / Q000235:genetics; D008954:Models, Biological; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D034741:RNA, Small Interfering / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics; D015203:Reproducibility of Results; D000075383:S100 Calcium Binding Protein A6; D009418:S100 Proteins / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D051901:Smad4 Protein / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000235:genetics; D051153:Wnt Proteins / Q000235:genetics / Q000502:physiology; D051176:beta Catenin / Q000235:genetics; D020830:rac1 GTP-Binding Protein / Q000235:genetics* / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; C485671:BAMBI protein, human; C486381:CITED2 protein, human; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D037483:Galectin 1; C445499:LGALS1 protein, human; D008565:Membrane Proteins; D008840:Microfilament Proteins; C449091:NKD1 protein, human; C107953:RAC1 protein, human; D034741:RNA, Small Interfering; D012097:Repressor Proteins; D000075383:S100 Calcium Binding Protein A6; D009418:S100 Proteins; C497796:SMAD4 protein, human; D051901:Smad4 Protein; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; D051153:Wnt Proteins; D051176:beta Catenin; C055351:S100A6 protein, human; C071058:moesin; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); C060932:MMP7 protein, human; D020783:Matrix Metalloproteinase 7; D020830:rac1 GTP-Binding Protein