结直肠癌（CRC）是胃肠道中常见的恶性肿瘤。结直肠癌的发生常与慢性炎症相关，肠上皮屏障对引起肠炎的感染和损伤起着重要的保护作用。研究表明转化生化因子β（TGF-β）信号通路在结直肠癌发生发展中具有早期抑癌、晚期促癌的双重功能，但对这种双重作用的调控机制尚不清楚。我们的前期研究发现，五羟色胺（5-HT）通过与肠道上皮细胞中的五羟色胺2B受体（5-HT2B）结合，对炎性相关结直肠癌（CAC）有早期抑癌、晚期促癌的双重调控作用，且初步发现这种双重作用可能是通过调控TGF-β信号通路来实现的。本项目将在此研究基础上，明确5-HT对CAC肿瘤发生发展的双重作用，揭示5-HT通过5-HT2B对TGF-β信号通路的调控机制，阐明5-HT调控肠道肿瘤的分子机制。本项目的实施将为5-HT的功能提供一个新认识，对肠道肿瘤的治疗提供新思路。

Colorectal cancer (CRC) is the most common cancer of the gastrointestinal tract. CRC is frequently associated with chronic inflammation, with the intestinal epithelial cell barrier playing an important protective role against the epithelial infections and injuries that cause colitis. Previous studies have demonstrated that transforming growth factor beta (TGF-β) signaling has a dual function in colorectal tumorigenesis, but the underlying mechanism for the dual function is unclear. Our preliminary studies have shown that 5-HT has a dual function in colitis-associated cancer (CAC) tumorigenesis through binding to 5-HT2B in intestinal epithelial cells, and preliminary verified that this dual function may be achieved through the regulation of TGF-β signaling pathway. On the basis of these data, we will further investigate the regulatory role of 5-HT in colorectal tumorigenesis, and dissect out the mechanisms underlying the dual roles of 5- HT in the regulation of colorectal tumor. We believe this project will provide new understanding to 5-HT function and a new approach to treatment of colorectal cancer.