Wnt/GSK‐3β mediates posttranslational modifications of FLYWCH1 to regulate intestinal epithelial function and tumorigenesis in the colon

This is the authors' abstract. We don't add key points for this paper.

Wnt/GSK-3β mediates posttranslational modifications of FLYWCH1 to regulate intestinal epithelial function and tumorigenesis in the colonThe intestinal epithelium undergoes rapid renewal, with the entire epithelial layer replaced within five days.Intestinal stem cells (ISCs), located in the intestinal crypts, generate all differentiated cell types necessary for intestinal function.Key signalling pathways involved in stem cell maintenance include Wnt, Notch, Hedgehog, and BMP.Wnt signalling, primarily driven by crypt cells, creates a signalling gradient to maintain homeostasis [1].However, nuclear β-catenin, the key regulator of Wnt signalling, correlates positively with tumorigenesis.While crypt base cells also exhibit high levels of nuclear βcatenin, the regulatory mechanism in normal tissue versus tumor remains unclear [1].FLYWCH-Type Zinc Finger 1 (FLYWCH1), an uncharacterised transcription factor, binds unphosphorylated-β-catenin [2], is associated with H3K9me3 in (peri)centromeric chromatin [3], and colocalizes with γ-H2AX foci [4].While its deletion is embryonically lethal in mice [5], the specific role and regulation of FLYWCH1 in tissue homeostasis and tumorigenesis remain unclear.This study investigates the role of FLYWCH1 in intestinal stem cell regulation and its impact on colorectal cancer.We hypothesize that FLYWCH1 directly influences ISC function by modulating critical signalling pathways, thereby playing a significant role in the initiation and progression of colorectal cancer (CRC).To assess the significance of FLYWCH1 expression in intestinal tissue homeostasis, we first examined its expression in murine tissues.Data from BioGPS (http://biogps. org) and the mouse gene expression database indicate vary-List of abbreviations: CHX, cycloheximide; Co-IP, co-immunoprecipitation; CRC, colorectal cancer;