创新结直肠癌防控治策略需要以全面和深入阐明结直肠癌发生发展分子机制为基础。目前普遍认为肠癌起源于肠道干细胞的异常，而肠道干细胞巢维持肠道干细胞的稳态，其失调在肠癌发生发展中发挥重要作用。我们前期研究结果显示，血管生成素（angiogenin，ANG，一种新发现的干细胞调控因子）可抑制肠癌发生，且可能是由肠道干细胞巢分泌而作用于肠道干细胞，但具体的作用、机制及其临床意义有待进一步阐明。为此，本项目将结合小鼠肠癌模型以及临床和人群队列样本，利用生化、分子和细胞生物学等手段，一方面阐释ANG在肠癌发生中的抑制作用及分子机制；另一方面揭示ANG及其作用通路在肠癌防治及早期诊断中的意义。我们认为，这些信息不仅有助于揭示ANG新功能新机制，更可为结直肠癌的防控治提供新思路新途径。

Fully understanding the molecular mechanism of colorectal cancer (CRC) initiation and progression is the basis for innovating CRC prevention, control, and therapeutic strategies. It is generally accepted that CRC originates from intestinal stem cell (ISC) abnormalities, while the ISC niche plays key role in maintaining ISC homeostasis. Intriguingly, our preliminary results revealed that angiogenin (ANG), a potential stem cell regulatory factor, suppressed the initiation of CRC in mouse model, possibly through the ISC niche-secreted ANG which then acts on ISC. However, its role, its underlying molecular mechanism, and its clinical significance remain to be clarified. In this proposal, we will integrate CRC mouse model, clinical samples and population cohort, to investigate the suppression effect and underlying molecular mechanism of ANG in the initiation of CRC with molecular, cellular, and pathophysiological techniques, and further explore the potential application of ANG in prevention and treatment of CRC. We believe this project will not only deepen our understanding of the functions and mechanisms of ANG, but also help to develop novel prevention, control, and therapeutic measures for CRC.