AXIN1

This study characterized the genomic landscape of leiomyosarcoma, a rare and aggressive tumor, by analyzing a large dataset from the AACR Project GENIE. Researchers examined over 1,000 tumor samples, identifying the most frequent somatic mutations and copy number alterations. TP53, RB1, and ATRX were the most commonly altered genes, with homozygous deletions of RB1 and TP53, and MAP2K4 amplifications. The study also highlighted enriched IGF2 and AXIN1 alterations in metastatic samples, suggesting their potential role in disease progression. These findings enhance the understanding of leiomyosarcoma biology and could guide future precision oncology strategies.

This study demonstrates that MEK1/2 inhibitors, targeting the Ras-MAPK pathway, induce AXIN1 protein loss in colorectal cancer cell lines and patient-derived organoids. Unlike GSK3 inhibitors, this loss is not attributed to altered AXIN1 protein stability or post-translational modifications, nor to a significant reduction in its transcript levels. Analyses revealed that MEK1/2 inhibitors reduce global protein synthesis via an mTOR-associated pathway, an effect sufficient to cause AXIN1 loss. Co-treatment with tankyrase inhibitors was shown to partially prevent this AXIN1 reduction.