Hardwick James C, Kodach Liudmila L, Offerhaus G Johan, van den Brink Gijs R
Department of Gastroenterology & Hepatology, Leiden University Medical Center, Leiden, the Netherlands.
Nat Rev Cancer. 2008 Oct;8(10):806-12. doi: 10.1038/nrc2467. Epub 2008 Aug 29.
Much of the current understanding of colorectal cancer stems from the study of rare, inherited colorectal cancer syndromes. Mutations in the bone morphogenetic protein (BMP) pathway have been found in juvenile polyposis, an inherited polyposis syndrome that predisposes to colorectal cancer. The hamartomas that develop in these patients and in BMP pathway mutant mice have a remarkable mesenchymal component. Further evidence in mice suggests a primary role for mesenchymal loss of BMP signalling in hamartoma development. Here, we examine this evidence and question its relevance to sporadic colorectal carcinogenesis.
目前对结直肠癌的许多认识源于对罕见的遗传性结直肠癌综合征的研究。在青少年息肉病(一种易患结直肠癌的遗传性息肉病综合征)中发现了骨形态发生蛋白(BMP)信号通路的突变。这些患者以及BMP信号通路突变小鼠中发生的错构瘤具有显著的间充质成分。小鼠实验的进一步证据表明,间充质中BMP信号缺失在错构瘤形成中起主要作用。在此,我们审视这一证据,并质疑其与散发性结直肠癌发生的相关性。