National Translational Science Center for Molecular Medicine and Department of Cell Biology, Fourth Military Medical University, Xi'an 710032, Shaanxi, China.
Department of Pulmonary and Critical Care Medicine, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, Shaanxi, China.
Cell Metab. 2021 Jan 5;33(1):160-173.e6. doi: 10.1016/j.cmet.2020.12.010.
CD147 is a tumor-associated glycoprotein that regulates cell metabolism. However, CD147 methylation and its subsequent role in cancer cell metabolism remain unclear. Here, we detect CD147 di-methylation in 16 non-small-cell lung cancer (NSCLC) tissues using liquid chromatography-tandem mass spectrometry. CD147 is di-methylated to CD147-K234me2 by lysine methyltransferase 5A (KMT5A). The increase in KMT5A expression boosts the levels of CD147-K234me2, further promoting the interaction between CD147 and monocarboxylate transporter 4 (MCT4), which enhances the translocation of MCT4 from the cytoplasm to the membrane. Overexpression of CD147-K234me2 and KMT5A enhances glycolysis and lactate export in NSCLC cells. Clinical analysis shows that high CD147-K234me2 expression is significantly related to cancer progression and overall survival, and has prognostic significance in individuals with NSCLC, especially for those in the early stages. Our findings indicate that CD147-K234me2 plays a critical role in cancer metabolism, and it can be a highly promising therapeutic target for NSCLC.
CD147 是一种肿瘤相关糖蛋白，可调节细胞代谢。然而，CD147 甲基化及其在癌细胞代谢中的后续作用尚不清楚。在这里，我们使用液相色谱-串联质谱法在 16 例非小细胞肺癌（NSCLC）组织中检测到 CD147 二甲基化。赖氨酸甲基转移酶 5A（KMT5A）将 CD147 二甲基化为 CD147-K234me2。KMT5A 表达的增加会提高 CD147-K234me2 的水平，从而进一步促进 CD147 与单羧酸转运蛋白 4（MCT4）的相互作用，增强 MCT4 从细胞质向膜的易位。CD147-K234me2 和 KMT5A 的过表达增强了 NSCLC 细胞中的糖酵解和乳酸外排。临床分析表明，高 CD147-K234me2 表达与癌症进展和总生存期显著相关，对 NSCLC 患者具有预后意义，尤其是早期患者。我们的研究结果表明，CD147-K234me2 在癌症代谢中起着关键作用，它可能是 NSCLC 的一个极具前景的治疗靶点。
