期刊
CANCER CELL INTERNATIONAL
卷 23, 期 1, 页码 -出版社
BMC
DOI: 10.1186/s12935-023-02973-z
关键词
Colorectal cancer; Age; Methylmalonic acid; Epithelial-mesenchymal transition; Wnt; beta-catenin
类别
This study investigated the role of upregulated metabolites of aged serum in colorectal cancer (CRC) progression. Methylmalonic acid (MMA) was found to be responsible for tumorigenesis and metastasis in CRC. Through Wnt/beta-catenin signaling pathway mediated epithelial-mesenchymal transition (EMT), MMA promoted CRC progression. These findings highlight the importance of age-related metabolic reprogramming in CRC and suggest a potential therapeutic target for elderly patients.
Background It has been manifested in several studies that age-related metabolic reprogramming is associated with tumor progression, in particular, colorectal cancer (CRC). Here we investigated the role of upregulated metabolites of the aged serum, including methylmalonic acid (MMA), phosphoenolpyruvate (PEP), and quinolinate (QA), in CRC. Methods Functional assays including CCK-8, EdU, colony formation and transwell experiments were used to ascertain which upregulated metabolite of elderly serum was related to tumor progression. RNA-seq analysis was conducted to explore the potential mechanisms of MMA-induced CRC progression. Subcutaneous tumorigenesis and metastatic tumor models were constructed to verify the function of MMA in vivo. Results Among three consistently increased metabolites of the aged sera, MMA was responsible for tumorigenesis and metastasis in CRC, according to functional assays. The promotion of Epithelial-mesenchymal transition (EMT) was observed in CRC cells treated with MMA, on the basis of protein expression of EMT markers. Moreover, combined with transcriptome sequencing, Wnt/beta-catenin signaling pathway was activated in CRC cells treated with MMA, which was verified by western blot and qPCR experiments. Furthermore, animal assays demonstrated the pro-proliferation and promotion of metastasis role of MMA in vivo. Conclusion We have identified that age-dependent upregulation of MMA in serum promoted the progression of CRC via Wnt/beta-catenin signaling pathway mediated EMT. These collective findings provide valuable insights into the vital role of age-related metabolic reprogramming in CRC progression and propose a potential therapeutic target for elderly CRC.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据