角蛋白KRT17通过调控STAT3/NF-κB信号通路促进胃癌腹膜转移的机制研究

腹膜转移是胃癌最常见的转移模式，预后极差且发生机制未明。深入探索胃癌腹膜转移发生机制具有重要意义。我们通过转录组测序筛选出差异表达基因，首次发现角蛋白17（KRT17）在腹膜转移灶和原发灶高表达。KRT17高表达的胃癌患者预后更差，更容易发生腹膜转移。体内体外实验发现KRT17能促进胃癌的增殖和迁移，敲减KRT17可降低胃癌腹膜转移瘤形成。此外，KRT17可能通过与STAT3结合并激活NF-κB通路。为此，我们提出“KRT17可能通过与STAT3结合并激活NF-κB通路，进而促进胃癌增殖迁移能力，并促进胃癌腹膜转移”的科学假设。但是，具体分子机制未明。本项目拟明确KRT17在胃癌腹膜转移中的作用；阐明KRT17调控STAT3/NF-κB通路的分子机制；探索靶向KRT17抑制胃癌腹膜转移效应。本项目将阐明胃癌腹膜转移发生发展的分子机制，为寻找预测胃癌腹膜转移标记物以及治疗靶点提供理论依据。

Peritoneal metastasis is the most common metastatic mode of gastric cancer, with extremely poor prognosis and unknown mechanism. Therefore, it is of great significance to further explore the mechanism of peritoneal metastasis in gastric cancer. We performed RNA sequencing and identify the differentially expressed genes for peritoneal metastasis in gastric cancer. We firstly identified that keratin 17 (KRT17) is highly expressed in peritoneal metastases and primary lesion. Gastric cancer patients with high KRT17 expression have worse prognosis and are more prone to peritoneal metastasis. In vivo and in vitro experiments showed that KRT17 could promote the proliferation and migration of gastric cancer cell, and knockdown of KRT17 could reduce the formation of peritoneal metastases of gastric cancer. In addition, KRT17 may activate the NF-κB pathway by binding to STAT3.Therefore, we proposed the hypothesis that "KRT17 may promote the proliferation and migration ability of gastric cancer by binding to STAT3 and activating NF-κB pathway, thereby promoting the peritoneal metastasis of gastric cancer". However, the molecular mechanism is unclear. Therefore, this project aims to clarify the role of KRT17 in peritoneal metastasis of gastric cancer, to elucidate the molecular mechanism of KRT17 regulating STAT3/NF-κB pathway, and to explore the inhibition effect of targeted KRT17 on peritoneal metastasis of gastric cancer. In summary, this project will clarify the molecular mechanism of the occurrence and development of peritoneal metastasis in gastric cancer, and provide a theoretical basis for identifying the biomarkers and therapeutic targets for predicting gastric cancer peritoneal metastasis.