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Microenvironment-induced changes in expression of tumor-promoting RAC1B in colorectal cells

2020-03-03Conference object Restricted access
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dc.contributor.authorPereira, Joana
dc.contributor.authorGonçalves, Vânia
dc.contributor.authorMatos, Paulo
dc.contributor.authorJordan, Peter
dc.date.accessioned2021-03-13T09:22:14Z
dc.date.available2021-03-13T09:22:14Z
dc.date.issued2020-03-03
dc.description.abstractIntroduction: An inflammatory microenvironment is a tumor-promoting condition that provides survival signals to which cancer cells respond with changes in their gene expression. One key gene regulatory mechanism that responds to extracellular signals is alternative splicing. For example RAC1B, a RAC1 alternative splicing variant, that we previously identified in a subset of BRAF-mutated colorectal tumors, was found increased in samples from inflammatory bowel disease patients or following experimentally-induced acute colitis in a mouse model.The main goal of this work is to determine the pro-inflammatory signals from stromal cells that lead to increased RAC1B expression in colorectal cells. Material and Methods: Caco-2 colorectal cells were either grown as polarized cell monolayer on porous filter membranes and then co-cultured with different stromal cell lines (fibroblasts, monocytes and macrophages) or grown as cysts in 3D matrices. RAC1B expression was analyzed by RT-PCR, Western blot and confocal fluorescence microscopy. Results and Discussions: Culture conditions for polarized 2D and 3D models were established as physiologically more relevant colon cell models. Co-culture experiments with polarized cells revealed that the presence of fibroblasts and/or M1 macrophages induced a transient increase in RAC1B protein levels in the colorectal cells, accompanied by a progressive loss of epithelial organization. The cytokines secreted by stromal cells are currently being identified. Conclusion: Our data indicate that extracellular signals from stromal cells can affect gene expression in colorectal cancer cells. The observed increase in alternatively spliced RAC1B will help to understand the tumor-promoting effect of inflammation and identify novel therapeutic strategies.pt_PT
dc.description.sponsorshipGrants UID/MULTI/04046/2019, SFRH/BD/109162/2015 and PTDC/BIA-MOL/28386/2017 from FCTpt_PT
dc.description.versionN/Apt_PT
dc.identifier.urihttp://hdl.handle.net/10400.18/7432
dc.language.isoengpt_PT
dc.relationBiosystems & Integrative Sciences Institute
dc.relationEffect of an inflammatory microenvironment on alternative splicing-mediated gene expression plasticity in colorectal cells
dc.relationMicroenvironmental effects on alternative splicing in malignant progression of colorectal tumor cells
dc.subjectTumor Microenvironmentpt_PT
dc.subjectAlternative Splicingpt_PT
dc.subjectRAC1Bpt_PT
dc.subjectColoretal Cancerpt_PT
dc.subjectCaco-2 cellspt_PT
dc.subjectCo-culturept_PT
dc.subjectMacrophagept_PT
dc.subjectVias de Transdução de Sinal e Patologias Associadaspt_PT
dc.titleMicroenvironment-induced changes in expression of tumor-promoting RAC1B in colorectal cellspt_PT
dc.typeconference object
dspace.entity.typePublication
oaire.awardTitleBiosystems & Integrative Sciences Institute
oaire.awardTitleEffect of an inflammatory microenvironment on alternative splicing-mediated gene expression plasticity in colorectal cells
oaire.awardTitleMicroenvironmental effects on alternative splicing in malignant progression of colorectal tumor cells
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UID%2FMulti%2F04046%2F2019/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//SFRH%2FBD%2F109162%2F2015/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FBIA-MOL%2F28386%2F2017/PT
oaire.citation.conferencePlaceLisboa, Portugalpt_PT
oaire.citation.titleEACR-AACR-ASPIC conference on Tumor Microenvironment, 2-4 March 2020pt_PT
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStream3599-PPCDT
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsclosedAccesspt_PT
rcaap.typeconferenceObjectpt_PT
relation.isProjectOfPublication35168786-8dfc-4a00-9759-dab3669fe1ae
relation.isProjectOfPublicationa70bea5c-3110-4af1-8e2a-dc548ed7b0e3
relation.isProjectOfPublication04d4989e-a18e-4287-bc19-a3d9ee1c7430
relation.isProjectOfPublication.latestForDiscovery04d4989e-a18e-4287-bc19-a3d9ee1c7430

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