ER stress transcription factor Xbp1 suppresses intestinal tumorigenesis and directs intestinal stem cells

Abstract

X-box–binding protein 1 suppresses tumor formation in the gut by regulating Ire1α and Stat3-mediated regenerative responses in the epithelium as a consequence of ER stress.

Opposing unfolded-protein-response signals converge on death receptor 5 to control apoptosis

“…Conversely, XBP1s knockdown — which led to compensatory IRE1α hyperphosphorylation (Fig. 4D) as reported (22) — accelerated DR5 mRNA decay and diminished DR5 upregulation, caspase-8 activation and apoptosis (Fig. 4 B, D and E, and fig.…”

Akkermansia muciniphila induces gut microbiota remodelling and controls islet autoimmunity in NOD mice

“…Consistent with this, there was a trend towards increased distance between luminal bacteria and epithelial cells (online supplementary figure S3). Expression of the immunoglobulin binding protein BiP was downregulated and a trend was seen for downregulation of X-box binding protein-1 Xbp1,28 both sensors of - endoplasmic reticulum-associated stress in intestinal epithelial cells (figure 4G). These epithelial homeostasis-related phenomena in the gut also reflected beneficially to endotoxin levels in the serum, which were significantly lower in A. muciniphila -treated mice (figure 4H).…”

Type I interferon signalling in the intestinal epithelium affects Paneth cells, microbial ecology and epithelial regeneration

“…Intestinal hyperproliferation as a response to intestinal injury can associate with subsequent tumourigenesis,37 48 49 which is thought to contribute to the increased propensity to develop tumours over time in patients with IBD 50. We therefore wondered whether increased IEC turnover observed in Ifnar1 −/−(IEC) compared with Ifnar1 +/+(IEC) mice, when housed separately, may associate with an increased propensity to develop colitis-associated tumours.…”

“…Increased proliferation and turnover of IECs can have a variety of underlying causes,14 but commonly represents a uniform reaction to epithelial injury that, in case it is sustained, lays the ground for an increased propensity to tumour formation 48 49. Indeed, we observed increased tumour burden in Ifnar1 −/−(IEC) compared with Ifnar1 +/+(IEC) mice in the AOM/DSS model, a well-established murine model of colitis-associated cancer 29 30.…”