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dc.contributor.authorDopeso, H
dc.contributor.authorRodrigues, P
dc.contributor.authorBilic, J
dc.contributor.authorBazzocco, S
dc.contributor.authorCarton-Garcia, F
dc.contributor.authorMacaya, I
dc.contributor.authorGuimaraes de Marcondes, P
dc.contributor.authorAnguita, E
dc.contributor.authorMasanas, M
dc.contributor.authorJimenez-Flores, LM
dc.contributor.authorMartinez-Barriocanal, A
dc.contributor.authorNieto, R
dc.contributor.authorSegura, MF
dc.contributor.authorSchwartz, S
dc.contributor.authorMariadason, JM
dc.contributor.authorArango, D
dc.date.accessioned2020-12-18T03:55:04Z
dc.date.available2020-12-18T03:55:04Z
dc.date.issued2018-01-09
dc.identifierpii: bjc2017420
dc.identifier.citationDopeso, H., Rodrigues, P., Bilic, J., Bazzocco, S., Carton-Garcia, F., Macaya, I., Guimaraes de Marcondes, P., Anguita, E., Masanas, M., Jimenez-Flores, L. M., Martinez-Barriocanal, A., Nieto, R., Segura, M. F., Schwartz, S., Mariadason, J. M. & Arango, D. (2018). Mechanisms of inactivation of the tumour suppressor gene RHOA in colorectal cancer. BRITISH JOURNAL OF CANCER, 118 (1), pp.106-116. https://doi.org/10.1038/bjc.2017.420.
dc.identifier.issn0007-0920
dc.identifier.urihttp://hdl.handle.net/11343/255976
dc.description.abstractBACKGROUND: Reduced RHOA signalling has been shown to increase the growth/metastatic potential of colorectal tumours. However, the mechanisms of inactivation of RHOA signalling in colon cancer have not been characterised. METHODS: A panel of colorectal cancer cell lines and large cohorts of primary tumours were used to investigate the expression and activity of RHOA, as well as the presence of RHOA mutations/deletions and promoter methylation affecting RHOA. Changes in RHOA expression were assessed by western blotting and qPCR after modulation of microRNAs, SMAD4 and c-MYC. RESULTS: We show here that RHOA point mutations and promoter hypermethylation do not significantly contribute to the large variability of RHOA expression observed among colorectal tumours. However, RHOA copy number loss was observed in 16% of colorectal tumours and this was associated with reduced RHOA expression. Moreover, we show that miR-200a/b/429 downregulates RHOA in colorectal cancer cells. In addition, we found that TGF-β/SMAD4 upregulates the RHOA promoter. Conversely, RHOA expression is transcriptionally downregulated by canonical Wnt signalling through the Wnt target gene c-MYC that interferes with the binding of SP1 to the RHOA promoter in colon cancer cells. CONCLUSIONS: We demonstrate a complex pattern of inactivation of the tumour suppressor gene RHOA in colon cancer cells through genetic, transcriptional and post-transcriptional mechanisms.
dc.languageEnglish
dc.publisherNATURE PUBLISHING GROUP
dc.rights.urihttps://creativecommons.org/licenses/by-nc-sa/4.0
dc.titleMechanisms of inactivation of the tumour suppressor gene RHOA in colorectal cancer
dc.typeJournal Article
dc.identifier.doi10.1038/bjc.2017.420
melbourne.affiliation.departmentMedicine (Austin & Northern Health)
melbourne.affiliation.facultyMedicine, Dentistry & Health Sciences
melbourne.source.titleBritish Journal of Cancer
melbourne.source.volume118
melbourne.source.issue1
melbourne.source.pages106-116
dc.rights.licenseCC BY-NC-SA
melbourne.elementsid1295295
melbourne.contributor.authorMariadason, John
dc.identifier.eissn1532-1827
melbourne.accessrightsOpen Access


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