2. Academic Validation
  3. AMT inhibits the progression of non-small cell lung cancer by suppressing the PI3K/AKT/GSK-3β/β-catenin pathway via H3K27me3 regulation

AMT inhibits the progression of non-small cell lung cancer by suppressing the PI3K/AKT/GSK-3β/β-catenin pathway via H3K27me3 regulation

  • Eur J Pharmacol. 2026 Jan 12:1011:178460. doi: 10.1016/j.ejphar.2025.178460.
Yixing Gao 1,  Guoji E 2,  Lan Feng 2,  Ping Gan 3,  Shirui Huang 3,  Ziyi Tang 3,  Qian Liang 1,  Yan Wang 4,  Yuqi Gao 3,  Erlong Zhang 5
Affiliations

Affiliations

  • 1 Institute of Cancer, Xinqiao Hospital, Army Medical University, Chongqing, China; Chongqing Key Laboratory of Immunotherapy, Chongqing, China.
  • 2 Institute of Medicine and Equipment for High Altitude Region, College of High Altitude Military Medicine, Army Medical University, Chongqing, China; Key Laboratory of Extreme Environmental Medicine, Ministry of Education of China, Chongqing, China.
  • 3 Institute of Medicine and Equipment for High Altitude Region, College of High Altitude Military Medicine, Army Medical University, Chongqing, China; Key Laboratory of Extreme Environmental Medicine, Ministry of Education of China, Chongqing, China; Yu-Yue Pathology Scientific Research Center and Jinfeng Laboratory, Chongqing, China.
  • 4 Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, China.
  • 5 Institute of Medicine and Equipment for High Altitude Region, College of High Altitude Military Medicine, Army Medical University, Chongqing, China; Key Laboratory of Extreme Environmental Medicine, Ministry of Education of China, Chongqing, China. Electronic address: [email protected].
PMID: 41354296 DOI: 10.1016/j.ejphar.2025.178460
Abstract

Reprogramming of glycine metabolism is closely associated with Cancer initiation and progression. The mRNA and protein expression of aminomethyltransferase (AMT), an enzyme of the glycine cleavage system, is decreased in human non-small cell lung Cancer (NSCLC) and is associated with poor prognosis. AMT overexpression significantly impaired the proliferation, migration and drug resistance of NSCLC cells. Further results demonstrated that the upregulation of AMT inhibits NSCLC progression in vivo. Moreover, the suppressive effect of AMT on NSCLC cells occurred through the downregulation of PI3K/Akt/GSK-3β/β-catenin signaling. And AMT overexpression reduces the expression of PI3K and Akt1 by increasing the level of H3K27me3. This work reveals that the negative role of AMT in regulating NSCLC progression, which emerges potential therapeutic implications.

Keywords

AMT; H3K27me3; Malignant phenotype; NSCLC; PI3K.

Figures
Products
Inhibitors & Agonists
Other Products