Bottom-up or Top-down: Inflammation Reprograms Paneth Cells to Develop Bowel Cancers

LGR5型 干细胞 癌症干细胞 生物 潘尼斯电池 癌变 祖细胞 地穴 结直肠癌 背景(考古学) 癌症 癌症研究 免疫学 细胞生物学 遗传学 小肠 内分泌学 古生物学
作者
Julian Chua,Alex Gregorieff,Arshad Ayyaz
出处
期刊:Cancer Research [American Association for Cancer Research]
卷期号:84 (20): 3324-3326
标识
DOI:10.1158/0008-5472.can-24-3073
摘要

The origins of colorectal cancer have long been a subject of intense debate. Early observations noted cancer formation in the human gut slightly above the base of crypts, the structural and functional units of the regenerative compartment of the intestinal epithelium. This suggested that the cells of origin for colorectal cancer reside close to the crypt–villus junction, where more differentiated cells are located. However, the specific induction of early cancer-initiating mutations within differentiated cells failed to initiate cancer. The subsequent identification of long-lived Lgr5+ intestinal stem cells and investigations into their role in cancer development further shifted the earlier views, leading to the widely accepted theory that colorectal cancer arises from stem cells and progenitors located at the base of crypts. A recent study published in Nature Genetics by Mathijs P. Verhagen and colleagues challenges this paradigm, providing compelling evidence that differentiated nonstem cell lineages, particularly Paneth cells, can serve as a source of intestinal tumorigenesis, especially in the context of inflammation and the consumption of a Western-style diet. This work significantly advances our understanding of the colorectal cancer initiation process and provides a new paradigm that may explain the increasingly higher incidence of colorectal cancer in younger people.
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