MTA1 coregulator regulates LDHA expression and function in breast cancer
MTA1 coregulator regulates LDHA expression and function in breast cancer
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DOI：
10.1016/j.bbrc.2019.09.078
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发表时间：
2019-11-26
影响因子：
3.1
通讯作者：
Pakala, Suresh B.
中科院分区：
文献类型：
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作者：
Guddeti, Rohith Kumar;Bali, Prerna;Pakala, Suresh B.
转移相关蛋白1（MTA 1）是一种染色质修饰剂，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仍然未被探索。在这里，我们报告说，MTA 1在葡萄糖代谢中具有重要作用，其中MTA 1调节LDHA表达和活性，随后其在乳腺癌运动中的功能。结果显示，乳腺癌患者中MTA 1的表达与LDHA的表达水平呈正相关。此外，发现MTA 1对于LDHA的最佳表达是必需的。潜在的分子机制涉及MTA 1与c-Myc的相互作用以及MTAl-c-Myc复合物在LDHA启动子上的募集以调节其转录。因此，在稳定表达MTA 1的MCF 7细胞中使用LDHA特异性siRNA敲低LDHA降低了MCF 7细胞的迁移。总之，这些发现揭示了MTA 1在LDHA表达及其产生的生物学功能中的调节作用。(C)2019爱思唯尔公司All rights reserved.
Metastasis Associated Proteinl (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 MTAl-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. (C) 2019 Elsevier Inc. All rights reserved.