结直肠癌（CRC）的起源长期以来一直是激烈争论的话题。早期观察发现，癌症在人类肠道中略高于隐窝基部的地方形成，隐窝是肠上皮再生区室的结构和功能单位。这表明结直肠癌的起源细胞位于隐窝-绒毛交界处附近，那里有更多分化的细胞。然而，在分化细胞内特异性诱导早期癌症引发突变未能引发癌症。随后对长寿命 Lgr5 肠道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早期的观点，导致了广泛接受的理论，即 CRC 起源于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》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，表明分化的非干细胞谱系，特别是潘氏细胞，可以作为肠道肿瘤发生的来源，特别是在炎症和肠道肿瘤的背景下。西式饮食的消费。这项工作极大地增进了我们对结直肠癌发生过程的理解，并提供了一个新的范例，可以解释年轻人结直肠癌发病率日益升高的原因。

The origins of colorectal cancer (CRC) 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 CRC 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 CRC 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 non-stem 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 CRC initiation process and provides a new paradigm that may explain the increasingly higher incidence of CRC in younger people.