在非小细胞肺癌中，BRG1通过促进SHP1介导的PKM2去磷酸化来抑制糖酵解。
BRG1 inhibits glycolysis by promoting SHP1-mediated dephosphorylation of PKM2 in non-small cell lung cancer.
作者信息
Zhan Wenli, Zhang Haokun, She Xiaowei, Zhang Genshan, Zhang Jiakun, Luo Xuelai, Li Haijie, Lan Jingqin
机构信息
Gastrointestinal Cancer Research Institute, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Thyroid and Breast Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
出版信息
Oncogenesis. 2025 Aug 24;14(1):32. doi: 10.1038/s41389-025-00577-y.
Glucose metabolic reprogramming serves as a regulatory mechanism to support tumor growth. Here, we identified that BRG1, a subunit of the SWI/SNF chromatin remodeling complex encoded by SMARCA4, can inhibit the glycolysis and proliferation of non-small cell lung cancer (NSCLC) cells. Mechanistically, BRG1 promotes the interaction between SHP1 and PKM2, which affects the subcellular localization and pyruvate kinase activity of PKM2 by reducing its phosphorylation at tyrosine 105 and facilitating PKM2 tetramer formation. Thus, we explored a novel biological function of BRG1 in NSCLC, elucidated the impact of BRG1 on glucose metabolism, and provided insights for clinical strategies targeting tumors with this genetic mutation.
葡萄糖代谢重编程作为一种支持肿瘤生长的调节机制。在此，我们发现由SMARCA4编码的SWI/SNF染色质重塑复合物的一个亚基BRG1可以抑制非小细胞肺癌（NSCLC）细胞的糖酵解和增殖。机制上，BRG1促进SHP1与PKM2之间的相互作用，通过减少PKM2在酪氨酸105处的磷酸化并促进PKM2四聚体形成，从而影响PKM2的亚细胞定位和丙酮酸激酶活性。因此，我们探索了BRG1在NSCLC中的一种新的生物学功能，阐明了BRG1对葡萄糖代谢的影响，并为针对这种基因突变的肿瘤的临床策略提供了见解。
Zotero 插件