Department of Surgery and Cancer, Imperial College London, London, UK.
St. Mark's Hospital, London, Harrow, UK.
Oncogene. 2018 Jan 4;37(1):1-7. doi: 10.1038/onc.2017.300. Epub 2017 Sep 4.
Small mothers against decapentaplegic (SMAD) proteins are a family of signal transduction molecules in transforming growth factor β (TGFβ) ligand pathways that have been found to have a key role in the pathogenesis of inflammatory bowel disease (IBD). Long standing IBD predisposes individuals to colitis-associated colorectal cancer (CAC), an entity that possess unique characteristics compared to hereditary and sporadic cancer. The ligands of the TGFβ super family along with SMADs have also been implicated in several aspects of colorectal cancer formation. SMAD proteins are shown to be involved in a number of potentially carcinogenic mechanisms such as altering gene transcription, controlling stem cell differentiation to causing epigenetic changes. Modulation of these proteins has emerged as a novel therapeutic intervention for IBD although its effect on carcinogenesis remains elusive. This account reviews available evidence linking SMAD proteins to CAC and explores the potential areas for future research in this area.
小 mothers against decapentaplegic（SMAD）蛋白是转化生长因子 β（TGFβ）配体途径中的一类信号转导分子，已被发现在炎症性肠病（IBD）的发病机制中具有关键作用。长期存在的 IBD 使个体易患结肠炎相关结直肠癌（CAC），与遗传性和散发性癌症相比，CAC 具有独特的特征。TGFβ 超家族的配体以及 SMAD 也与结直肠癌形成的几个方面有关。SMAD 蛋白被证明参与了许多潜在的致癌机制，如改变基因转录、控制干细胞分化导致表观遗传改变。这些蛋白的调节已成为治疗 IBD 的一种新的治疗干预措施，尽管其对致癌作用的影响仍不清楚。本报告综述了将 SMAD 蛋白与 CAC 联系起来的现有证据，并探讨了该领域未来研究的潜在领域。
