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Stroma cell-derived signals stimulate expression of tumor-promoting RAC1B in colorectal cells
Publication . Pereira, Joana; Matos, Paulo; Jordan, Peter
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
tumours, 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 that lead to increased RAC1B expression in colorectal cells.
Stroma cells stimulate colorectal tumor cells to increase expression of tumor-promoting RAC1b
Publication . Pereira, Joana; Matos, Paulo; Jordan, Peter
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 tumours, 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 that lead to increased RAC1b expression in
colorectal cells.
Signaling Pathways Driving Aberrant Splicing in Cancer Cells
Publication . Gonçalves, Vânia; Pereira, Joana; Jordan, Peter
Aberrant profiles of pre-mRNA splicing are frequently observed in cancer. At the molecular level, an altered profile results from a complex interplay between chromatin modifications, the transcriptional elongation rate of RNA polymerase, and effective binding of the spliceosome to the generated transcripts. Key players in this interplay are regulatory splicing factors (SFs) that bind to gene-specific splice-regulatory sequence elements. Although mutations in genes of some SFs were described, a major driver of aberrant splicing profiles is oncogenic signal transduction pathways. Signaling can affect either the transcriptional expression levels of SFs or the post-translational modification of SF proteins, and both modulate the ratio of nuclear versus cytoplasmic SFs in a given cell. Here, we will review currently known mechanisms by which cancer cell signaling, including the mitogen-activated protein kinases (MAPK), phosphatidylinositol 3 (PI3)-kinase pathway (PI3K) and wingless (Wnt) pathways but also signals from the tumor microenvironment, modulate the activity or subcellular localization of the Ser/Arg rich (SR) proteins and heterogeneous nuclear ribonucleoproteins (hnRNPs) families of SFs.
Stroma cells increase expression of tumor-promoting RAC1B in colorectal cancer cells
Publication . Pereira, Joana; Matos, Paulo; Jordan, Peter
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.
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Funding agency
Wellcome Trust
Funding programme
Genetic & Molecular Sciences
Funding Award Number
109162