Expression of tumour-related Rac1b antagonizes B-Raf-induced senescence in colorectal cells

Henriques, Andreia FA; Barros, Patrícia; Moyer, Mary; Matos, Paulo; Jordan, Peter

Publication

Expression of tumour-related Rac1b antagonizes B-Raf-induced senescence in colorectal cells

2015-12-28Journal article

dc.contributor.author	Henriques, Andreia FA
dc.contributor.author	Barros, Patrícia
dc.contributor.author	Moyer, Mary
dc.contributor.author	Matos, Paulo
dc.contributor.author	Jordan, Peter
dc.date.accessioned	2016-02-18T16:46:48Z
dc.date.available	2019-01-01T01:30:10Z
dc.date.issued	2015-12-28
dc.description	Erratum Cancer Lett. 2022 Dec 1;550:215936. doi: 10.1016/j.canlet.2022.215936. Epub 2022 Oct 11.
dc.description.abstract	Mutations in the BRAF oncogene have been identified as a tumor-initiating genetic event in mainly melanoma, thyroid and colon cancer, resulting in an initial proliferative stimulus that is followed by a growth arrest period known as oncogene-induced senescence (OIS). It remains unknown what triggers subsequent escape from OIS to allow further tumor progression. A previous analysis revealed that around 80% of colorectal tumors carrying a mutation in BRAF also overexpress splice variant Rac1b. We used normal NCM460 colonocytes as a model to express oncogenic B-Raf-V600E in the presence or absence of co-transfected Rac1b and then analyzed the effect on expression of senescence markers. When oncogenic B-Raf-V600E was expressed we observed the induction of the senescence-associated β-galactosidase and of the cell-cycle inhibitors p14, p15 and p21 whereas proliferation marker Ki67 was suppressed. Upon co-expression of splice variant Rac1b, but not of Rac1, the B-Raf-induced senescence phenotype was reverted and expression of the cell-cycle inhibitors downregulated in a reactive oxygen-species dependent manner. We thus provide evidence that co-expression of splice variant Rac1b counteracts B-Raf-induced senescence, indicating the selection for increased Rac1b expression as one potential mechanism by which colorectal tumor cells can escape from B-Raf-induced OIS.	pt_PT
dc.description.sponsorship	Fundação para a Ciência e Tecnologia, Portugal (center grant to BioISI (UID/MULTI/04046/2013), contract ‘FCT Investigator’ to P.M. and fellowship SFRH/BPD/ 94322/2013 to P.B	pt_PT
dc.identifier.citation	Cancer Lett. 2015 Dec 28;369(2):368-75. doi: 10.1016/j.canlet.2015.08.027. Epub 2015 Sep 1	pt_PT
dc.identifier.doi	10.1016/j.canlet.2015.08.027	pt_PT
dc.identifier.issn	0304-3835
dc.identifier.uri	http://hdl.handle.net/10400.18/3424
dc.language.iso	eng	pt_PT
dc.peerreviewed	yes	pt_PT
dc.publisher	Elsevier	pt_PT
dc.relation.publisherversion	http://www.sciencedirect.com/science/article/pii/S0304383515005686	pt_PT
dc.subject	Vias de Transdução de Sinal e Patologias Associadas	pt_PT
dc.subject	Cancro Coloretal	pt_PT
dc.subject	Rac1b	pt_PT
dc.subject	Signalling	pt_PT
dc.subject	Senescence	pt_PT
dc.subject	B-Raf	pt_PT
dc.subject	Colorectal Cancer	pt_PT
dc.subject	Tumor Progression	pt_PT
dc.title	Expression of tumour-related Rac1b antagonizes B-Raf-induced senescence in colorectal cells	pt_PT
dc.type	journal article
dspace.entity.type	Publication
oaire.awardURI	info:eu-repo/grantAgreement/FCT/5876/UID%2FMulti%2F04046%2F2013/PT
oaire.citation.endPage	375	pt_PT
oaire.citation.startPage	368	pt_PT
oaire.citation.title	Cancer Letters	pt_PT
oaire.citation.volume	369(2)	pt_PT
oaire.fundingStream	5876
project.funder.identifier	http://doi.org/10.13039/501100001871
project.funder.name	Fundação para a Ciência e a Tecnologia
rcaap.rights	embargoedAccess	pt_PT
rcaap.type	article	pt_PT
relation.isProjectOfPublication	dc84f768-e6f2-4eea-b294-6c8ebbd1a156
relation.isProjectOfPublication.latestForDiscovery	dc84f768-e6f2-4eea-b294-6c8ebbd1a156