{"database":"GEO","file_versions":[],"scores":null,"additional":{"omics_type":["Other"],"species":["Homo sapiens"],"gds_type":[" Non-coding RNA profiling by high throughput sequencing","Other"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE312196"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"MEK inhibition induces AXIN1 loss in colorectal cancer by mTOR associated suppression of protein synthesis [RiboSeq_HCT116]","description":"AXIN1 is a central regulatory hub of many oncogenic pathways in colorectal cancer (CRC). As the main scaffold protein and least abundant component of the beta-catenin destruction complex, changes in AXIN1 levels affect Wnt signaling output. We show that targeting the Ras-MAPK pathway by MEK1/2 inhibitors induces AXIN1 loss across a panel of CRC cell lines and patient-derived organoids. GSK3B inhibition similarly reduced AXIN1 levels, yet by distinct mechanisms. MEK1/2 causes a reduction of AXIN1 transcript levels, but neither affects protein stability nor post-translational modifications of AXIN1. In contrast, GSK3B inhibition induces rapid AXIN1 degradation. Prevention of AXIN1 loss by co-treatment with tankyrase inhibitors was much stronger for GSK3B than for MEK1/2 inhibition. Using isogenic CRC cell lines and murine intestinal organoids, we show that APC truncations strongly reduce basal AXIN1 levels, but do not alter dynamics of AXIN1 loss upon MEK1/2 inhibition. Polysome profiling and Ribo-Seq revealed that MEK1/2 inhibition reduces global protein synthesis via an mTOR dependent pathway. This translational repression is sufficient to cause significant AXIN1 loss, as treatment with mTOR inhibitors phenocopies the effect of MEK1/2 inhibitors. Our study demonstrates that AXIN1 protein homeostasis is critically controlled by Ras-MAPK signaling at the level of protein synthesis, and that MEK1/2 inhibitors cause AXIN1 loss by translational repression.","dates":{"publication":"2026/06/03"},"accession":"GSE312196","cross_references":{"GSM":["GSM9340250","GSM9340251","GSM9340249","GSM9340247","GSM9340248","GSM9340245","GSM9340246","GSM9340243","GSM9340244","GSM9340252","GSM9340242","GSM9340253"],"GPL":["21697"],"GSE":["312196"],"taxon":["Homo sapiens"],"PMID":["[42204589]"]}}