CDX2
基因沉默
癌变
结直肠癌
癌症研究
体内
糖酵解
医学
免疫组织化学
细胞生长
基因表达
生物
癌症
细胞生物学
内科学
生物化学
新陈代谢
基因
遗传学
同源盒
作者
Qingguo Li,Shaobo Mo,Xinxiang Li,Sanjun Cai
标识
DOI:10.1200/jco.2019.37.4_suppl.561
摘要
561 Background: The CDX2 expression is significantly decreased in colorectal cancer (CRC) tissues and lost its expression is associated with poor survival. However, the underline of this activity of CDX2 is not well understood. In the present study, we sought to determine the role of CDX2 in tumorigenesis, and elucidate the possible mechanism. Methods: The effect of CDX2 expression on proliferation of and glycolysis in CRC cells was assessed by altering its expression in vitro and in vivo. Mechanistic investigation was carried out using cell and molecular biological approaches. Human CRC tissues were also used to verify the relationship between CDX2 expression and glycolysis. Results: Forced CDX2 expression in CRC cells inhibited their proliferation and colony formation. In contrast, silencing CDX2 expression had the opposite effect, suggesting that CDX2 is a negative regulator of oncogenesis in CRC. Mechanistically, CDX2 negatively regulated the aerobic glycolysis, a process that contributed to tumor progression by providing energy source and building blocks for macromolecule synthesis. Consistent with this observation, an in vivo subcutaneous xenograft mouse model and in a series of patients (n=71) received PET/CT initial after diagnosed also confirmed the hypothesis that CDX2 is a negative regulator of glycolysis as reflected by the decreased 18 FDG uptake in PET/CT system. Furthermore, increased expression of CDX2 downregulated that of a glycolytic enzyme, phosphoglycerate mutase 1(PGAM1) in vitro. Moreover, there was a negative relationship between CDX2 and PGAM1 expression in human CRC tissues as determined by both RT-PCR and Immunohistochemistry. Luciferase analysis further indicated that CDX2 could inhibited PGAM1 promoter activity at dose dependent. Conclusions: The CDX2 inhibits cell proliferation, reprograms glucose metabolism by targeting PGAM1 expression in CRC, and the CDX2/PGAM1 axis constitutes potential prognostic predictors and therapeutic targets for CRC.
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