Publication
Microenvironment-induced changes in expression of tumor promoting Rac1b
| dc.contributor.author | Pereira, Joana | |
| dc.contributor.author | Gonçalves, Vânia | |
| dc.contributor.author | Matos, Paulo | |
| dc.contributor.author | Jordan, Peter | |
| dc.date.accessioned | 2020-06-07T18:00:40Z | |
| dc.date.available | 2020-06-07T18:00:40Z | |
| dc.date.issued | 2019-11-11 | |
| dc.description.abstract | 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. 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. Culture conditions for polarized 2D and 3D models were established as physiologically more relevant colon cell models. Coculture 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. 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.version | N/A | pt_PT |
| dc.identifier.uri | http://hdl.handle.net/10400.18/6951 | |
| dc.language.iso | eng | pt_PT |
| dc.subject | Colorectal Cancer | pt_PT |
| dc.subject | Inflammation | pt_PT |
| dc.subject | Rac1b | pt_PT |
| dc.subject | Vias de Transdução de Sinal e Patologias Associadas | pt_PT |
| dc.title | Microenvironment-induced changes in expression of tumor promoting Rac1b | pt_PT |
| dc.type | conference object | |
| dspace.entity.type | Publication | |
| oaire.citation.conferencePlace | Berlin, Germany | pt_PT |
| oaire.citation.title | Goodbye Flat Biology: Advancing 3D-based Models for Cancer Biology and Drug Discovery, 10-13 November 2019 | pt_PT |
| rcaap.rights | embargoedAccess | pt_PT |
| rcaap.type | conferenceObject | pt_PT |