Department of Gastrointestinal Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
China Welfare Association International Peace Maternal and Child Health Care Center, Shanghai, China.
J Immunol Res. 2021 Mar 15;2021:6618837. doi: 10.1155/2021/6618837. eCollection 2021.
Mitochondrial Pyruvate Carrier 1 (MPC1), one of the rate-limiting proteins involved in glycolysis metabolism, has been demonstrated as a tumor inhibitor in several cancers. This study was conducted with the aim of exploring the role and underlying mechanisms of MPC2 in colorectal cancer (CRC). Here, we found that MPC2 expression was decreased in CRC samples. According to the analysis on our TMA data, lower expression of MPC2 is correlated with a higher incidence of distant metastasis and lymph node invasion, bigger tumor size, low survival rate of patients, and advanced T stages. Functionally, in vivo/vitro experiments showed that MPC2 knockdown induced CRC cell proliferation and growth, while MPC2 overexpression inhibited the proliferation and growth of CRC. Further study demonstrated that MPC2 knockdown resulted in aerobic glycolysis in CRC cells. Similarly, MPC2 overexpression in CRC cells also caused inhibited aerobic glycolysis. Further study found that MPC2 knockdown in CRC cell lines activated the mTOR signaling pathway, and the addition of rapamycin reversed the promoting effect of MPC2 knockdown on CRC proliferation and glycolysis. Likewise, the addition of MHY1485 also reversed the MPC2 overexpression's role in hindering aerobic glycolysis in CRC cells. Collectively, our study established that low expression of MPC2 led to CRC growth as well as aerobic glycolysis through the regulation of the mTOR pathway in CRC cells, indicating a potential biomarker and therapy target for CRC.
线粒体丙酮酸载体 1（MPC1）是糖酵解代谢中涉及的限速蛋白之一，已被证明在几种癌症中是一种肿瘤抑制剂。本研究旨在探索 MPC2 在结直肠癌（CRC）中的作用和潜在机制。在这里，我们发现 MPC2 在 CRC 样本中的表达降低。根据我们的 TMA 数据分析，MPC2 表达降低与远处转移和淋巴结侵犯发生率较高、肿瘤较大、患者生存率较低和 T 分期较晚相关。功能上，体内/体外实验表明，MPC2 敲低诱导 CRC 细胞增殖和生长，而 MPC2 过表达抑制 CRC 的增殖和生长。进一步研究表明，MPC2 敲低导致 CRC 细胞中的有氧糖酵解。同样，CRC 细胞中 MPC2 的过表达也导致有氧糖酵解受到抑制。进一步的研究发现，MPC2 敲低在 CRC 细胞系中激活了 mTOR 信号通路，雷帕霉素的添加逆转了 MPC2 敲低对 CRC 增殖和糖酵解的促进作用。同样，添加 MHY1485 也逆转了 MPC2 过表达对 CRC 细胞中抑制有氧糖酵解的作用。总之，我们的研究表明，MPC2 表达降低通过调节 CRC 细胞中的 mTOR 通路导致 CRC 生长和有氧糖酵解，提示其作为 CRC 的潜在生物标志物和治疗靶点。
