自下而上还是自上而下?炎症重编程使肠细胞发展成肠癌

IF 12.5 1区 医学 Q1 ONCOLOGY
Julian Chua, Alex Gregorieff, Arshad Ayyaz
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引用次数: 0

摘要

长期以来,大肠癌(CRC)的起源一直是人们激烈争论的话题。早期观察发现,癌症形成于人体肠道隐窝基部稍上方,隐窝是肠上皮再生区的结构和功能单元。这表明,CRC 的起源细胞位于隐窝与绒毛交界处附近,那里的细胞分化程度较高。然而,在分化细胞中特异性诱导早期癌症诱发突变并不能诱发癌症。随后对长寿命 Lgr5+ 肠干细胞的鉴定以及对其在癌症发展中作用的研究进一步改变了先前的观点,从而形成了一种广为接受的理论,即 CRC 源自位于隐窝底部的干细胞和祖细胞。Mathijs P. Verhagen 及其同事最近在《自然-遗传学》(Nature Genetics)杂志上发表的一项研究挑战了这一范式,提供了令人信服的证据,证明分化的非干细胞系,尤其是Paneth细胞,可以作为肠道肿瘤发生的来源,特别是在炎症和西式饮食的背景下。这项研究极大地推动了我们对 CRC 发病过程的了解,并提供了一种新的范式,可以解释为什么 CRC 在年轻人中的发病率越来越高。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Bottom-up or Top-down: Inflammation Reprograms Paneth Cells to Develop Bowel Cancers.

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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来源期刊
Cancer research
Cancer research 医学-肿瘤学
CiteScore
16.10
自引率
0.90%
发文量
7677
审稿时长
2.5 months
期刊介绍: Cancer Research, published by the American Association for Cancer Research (AACR), is a journal that focuses on impactful original studies, reviews, and opinion pieces relevant to the broad cancer research community. Manuscripts that present conceptual or technological advances leading to insights into cancer biology are particularly sought after. The journal also places emphasis on convergence science, which involves bridging multiple distinct areas of cancer research. With primary subsections including Cancer Biology, Cancer Immunology, Cancer Metabolism and Molecular Mechanisms, Translational Cancer Biology, Cancer Landscapes, and Convergence Science, Cancer Research has a comprehensive scope. It is published twice a month and has one volume per year, with a print ISSN of 0008-5472 and an online ISSN of 1538-7445. Cancer Research is abstracted and/or indexed in various databases and platforms, including BIOSIS Previews (R) Database, MEDLINE, Current Contents/Life Sciences, Current Contents/Clinical Medicine, Science Citation Index, Scopus, and Web of Science.
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