Biology Division, Indian Institute of Science Education and Research (IISER) Tirupati, Karakambadi Road, Mangalam, Tirupati, 517507, Andhra Pradesh, India.
Department of Biochemistry, Indian Academy Degree College Autonomous, Hennur Main Road, Bengaluru, 560043, Karnataka, India.
Biochem Biophys Res Commun. 2019 Nov 26;520(1):54-59. doi: 10.1016/j.bbrc.2019.09.078. Epub 2019 Sep 27.
Metastasis Associated Protein1 (MTA1) is a chromatin modifier and its expression is significantly associated with prognosis of many cancers. However, its role in glucose metabolism remains unexplored. Here, we report that MTA1 has a significant role in glucose metabolism where MTA1 regulates the LDHA expression and activity and subsequently its function in breast cancer motility. The results showed that MTA1 expression is positively correlated with the LDHA expression levels in breast cancer patients. Further, it was found that MTA1 is necessary for the optimal expression of LDHA. The underlying molecular mechanism involves the interaction of MTA1 with c-Myc and recruitment of MTA1-c-Myc complex on to the LDHA promoter to regulate its transcription. Consequently, the LDHA knock down using LDHA specific siRNA in MCF7 cells stably expressing MTA1 reduced the migration of MCF7 cells. Altogether these findings revealed the regulatory role for MTA1 in LDHA expression and its resulting biological function.
转移相关蛋白 1（MTA1）是一种染色质修饰物，其表达与许多癌症的预后显著相关。然而，其在葡萄糖代谢中的作用尚未被探索。在这里，我们报告 MTA1 在葡萄糖代谢中具有重要作用，MTA1 调节 LDHA 的表达和活性，进而影响乳腺癌的运动性。结果表明，MTA1 的表达与乳腺癌患者的 LDHA 表达水平呈正相关。此外，研究还发现 MTA1 是 LDHA 最佳表达所必需的。潜在的分子机制涉及 MTA1 与 c-Myc 的相互作用，以及 MTA1-c-Myc 复合物募集到 LDHA 启动子上，以调节其转录。因此，在稳定表达 MTA1 的 MCF7 细胞中使用 LDHA 特异性 siRNA 敲低 LDHA，可降低 MCF7 细胞的迁移能力。总之，这些发现揭示了 MTA1 在 LDHA 表达及其生物学功能中的调节作用。
