2. Academic Validation
  3. BRG1 inhibits glycolysis by promoting SHP1-mediated dephosphorylation of PKM2 in non-small cell lung cancer

BRG1 inhibits glycolysis by promoting SHP1-mediated dephosphorylation of PKM2 in non-small cell lung cancer

  • Oncogenesis. 2025 Aug 24;14(1):32. doi: 10.1038/s41389-025-00577-y.
Wenli Zhan 1,  Haokun Zhang 1,  Xiaowei She 1,  Genshan Zhang 1,  Jiakun Zhang 1,  Xuelai Luo 1,  Haijie Li # 2,  Jingqin Lan # 3
Affiliations

Affiliations

  • 1 Gastrointestinal Cancer Research Institute, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • 2 Gastrointestinal Cancer Research Institute, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. hjli@tjh.tjmu.edu.cn.
  • 3 Department of Thyroid and Breast Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. jqlan@tjh.tjmu.edu.cn.
  • # Contributed equally.
PMID: 40849293 DOI: 10.1038/s41389-025-00577-y
Abstract

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.

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