谷氨酰胺代谢在结直肠癌发病中发挥重要作用，但具体机制尚未清楚。我们预实验研究发现谷氨酰胺代谢关键酶GLS1在结直肠癌细胞中高表达且可促进细胞增殖；敲低β-Catenin或HSF1表达可经由上调miR137转录来下调GLS1表达；β-Catenin可能协同HuR来调控HSF1翻译。因此推测β-Catenin可能通过HSF1来抑制miR137转录，间接上调GLS1表达，从而促进谷氨酰胺代谢。在本研究中，我们拟通过细胞和动物等实验来分析β-Catenin对HSF1翻译表达的调控作用及其机制，以及HSF1对miR137转录表达的调控作用和机制，从而阐明β-Catenin对GLS1表达的调控机制，明确β-Catenin-HSF1-miR137-GLS1信号轴在谷氨酰胺代谢以及结直肠癌发病中的作用及临床意义。因此，本研究将从代谢调控角度揭示结直肠癌的发病机制，从而为结直肠癌的有效防治提供新的思路。

Glutaminolysis plays a critical role in the pathogenesis of many cancers including colorectal cancer. However, the mechanism of glutaminolysis regulation in cancer cells remains largely undefined. In the preliminary studies for this proposed work we found that glutaminase1 (GLS1), one of the rate-limiting enzymes in glutaminolysis, was highly expressed and important for the growth of colorectal cancer cell. Moreover, we found that knockdown β-Catenin expression could down-regulate GLS1 expression through the up-regulation of GLS1-targeting miR137. Next, we found that β-Catenin might regulate HSF1 translation by directly interacting with HuR, and HSF1 could transcriptionally regulate miR137 expression. Therefore, we proposed that activated wnt/β-Catenin signaling could promote glutaminolysis and colorectal carcinogenesis via regulating HSF1-miR137-GLS1 axis. To approve this hypothesis, we will perform a series of in vitro and in vivo experiments to define the role of β-Catenin in the translation of HSF1 mRNA, explore the role of HSF1 in regulating miR137 transcription and clarify the clinical relevance of β-Catenin-HSF1-miR137-GLS1 axis in colorectal cancer. Taken together, we hope our proposed study will reveal the role and mechanism of Wnt/β-Catenin signaling in promoting glutaminolysis and colorectal carcinogenesis. By doing so, we believe it could facilitate the development of novel strategies for the effective prevention and treatment of colorectal cancer and probably other cancers.