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• W3089593963 abstract "Abstract Inflammation might substantially contribute to the limited therapeutic success of current systemic therapies in colorectal cancer (CRC). Amongst cytokines involved in CRC biology, the proinflammatory chemokine IL-8 has recently emerged as a potential prognostic/predictive biomarker. Here, we show that BRAF mutations and PTEN-loss are associated with high IL-8 levels in CRC models in vitro and that BRAF/MEK/ERK, but not PI3K/mTOR, targeting controls its production in different genetic contexts. In particular, we identified a BRAF/ERK2/CHOP axis affecting IL-8 transcription, through regulation of CHOP subcellular localization, and response to targeted inhibitors. Moreover, RNA Pol II and an open chromatin status in the CHOP-binding region of the IL-8 gene promoter cooperate towards increased IL-8 expression, after a selective BRAF inhibition. Overall, our data show that IL-8 production is finely and differentially regulated depending on the tumor genetic context and might be targeted for therapeutic purposes in molecularly defined subgroups of CRC patients." @default.
• W3089593963 created "2020-10-08" @default.
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• W3089593963 date "2020-10-01" @default.
• W3089593963 modified "2023-10-15" @default.
• W3089593963 title "BRAF status modulates Interelukin-8 expression through a CHOP-dependent mechanism in colorectal cancer" @default.
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• W3089593963 doi "https://doi.org/10.1038/s42003-020-01263-y" @default.
• W3089593963 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7530707" @default.
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