Linking microbiota changes and lipid signalling to tumour risk in models of unfolded protein response-driven colonic tumorigenesis (P11)

内质网未折叠蛋白反应（UPRER）与肠道炎症和癌症有关，但其在致癌组织转化中的因果作用仍不完全清楚。我们将UPRER激活转录因子6（ATF6）确定为结直肠癌和结肠炎相关癌症的新的临床相关靶点。上皮细胞中慢性激活的ATF6信号传导诱导脂质代谢的改变，包括长链脂肪酸的合成和肿瘤生态位中的微生物群适应。我们现在希望将脂质和微生物群信号传导与肿瘤发生机制联系起来，并更好地了解UPR相关肿瘤发生中的炎症。

The endoplasmic reticulum unfolded protein response (UPRER) is linked to intestinal inflammation and cancer, yet its causal role in oncogenic tissue transformation remains incompletely understood. We identified the UPRER activating transcription factor 6 (ATF6) as a novel and clinically relevant target of colorectal cancer and colitis-associated cancer. Chronically activated ATF6 signalling in the epithelium induced alterations in lipid metabolism, including the synthesis of long chain fatty acids, and microbiota adaptations in the tumour niche. We now want to mechanistically link lipid and microbiota signalling to tumour initiation, and better understand inflammation in UPR-related tumorigenesis.