| Autor: |
Manco M; Molecular Biotechnology Center, Department of Molecular Biotechnology and Health Sciences, University of Turin, 10126 Turin, Italy., Ala U; Department of Veterinary Science, University of Turin, Largo Paolo Braccini 2, 10095 Grugliasco, Italy., Cantarella D; Department of Oncology, University of Torino, S.P. 142, km 3.95, Torino, 10060 Candiolo, Italy., Tolosano E; Molecular Biotechnology Center, Department of Molecular Biotechnology and Health Sciences, University of Turin, 10126 Turin, Italy., Medico E; Department of Oncology, University of Torino, S.P. 142, km 3.95, Torino, 10060 Candiolo, Italy., Altruda F; Department of Veterinary Science, University of Turin, Largo Paolo Braccini 2, 10095 Grugliasco, Italy., Fagoonee S; Institute of Biostructure and Bioimaging, National Research Council (CNR) c/o Molecular Biotechnology Center, 10126 Turin, Italy. |
| Abstrakt: |
RNA binding proteins are well recognized as critical regulators of tumorigenic processes through their capacity to modulate RNA biogenesis, including alternative splicing, RNA stability and mRNA translation. The RNA binding protein Epithelial Splicing Regulatory Protein 1 (ESRP1) can act as a tumor suppressor or promoter in a cell type- and disease context-dependent manner. We have previously shown that elevated expression of ESRP1 in colorectal cancer cells can drive tumor progression. To gain further insights into the pro-tumorigenic mechanism of action of ESRP1, we performed cDNA microarray analysis on two colorectal cells lines modulated for ESRP1 expression. Intriguingly, RAC1b was highly expressed, both at mRNA and protein levels, in ESRP1-overexpressing cells, while the opposite trend was observed in ESRP1-silenced CRC cells. Moreover, RAC1 and RAC1b mRNA co-immunoprecipitate with ESRP1 protein. Silencing of RAC1b expression significantly reduced the number of soft agar colonies formed by ESRP1-overexpressing cells, suggesting that ESRP1 acted, at least partially, through RAC1b in its tumor-promoting activities in CRC cells. Thus, our data provide molecular cues on targetable candidates in CRC cases with high ESRP1 expression. |
