2. Academic Validation
  3. Transglutaminase 2 promotes breast cancer cell autophagy by targeting p53/ mTOR axis

Transglutaminase 2 promotes breast cancer cell autophagy by targeting p53/ mTOR axis

  • Biochem Pharmacol. 2025 Jul:237:116926. doi: 10.1016/j.bcp.2025.116926.
Jiasi Chen 1,  Mengxin Li 2,  Juanjuan Mao 1,  Xuanzhong Wang 3,  Baofeng Guo 4,  Xuyang Chen 5,  Dhan V Kalvakolanu 6,  Jinghui Hong 2,  Mei Yang 1,  Jixuan Liu 1,  Qian Luo 1,  Jiaying Yang 1,  Xinze Sun 1,  Yong Tian 1,  Ling Zhang 7
Affiliations

Affiliations

  • 1 College of Basic Medical Sciences, the Medical Basic Research Innovation Center of Airway Disease in North China, Key Laboratory of Pathobiology, Ministry of Education, and Department of Pathophysiology, Jilin University, Changchun 130021, China.
  • 2 Department of Breast Surgery, General Surgery Center, First Hospital of Jilin University, Changchun, China.
  • 3 Department of Radiation Oncology, First Hospital of Jilin University, Changchun, China.
  • 4 Department of Surgery, China-Japan Union Hospital of Jilin University, Changchun, China.
  • 5 School of Basic Medicine and Life Sciences, Hainan Medical University, Haikou, China.
  • 6 Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
  • 7 College of Basic Medical Sciences, the Medical Basic Research Innovation Center of Airway Disease in North China, Key Laboratory of Pathobiology, Ministry of Education, and Department of Pathophysiology, Jilin University, Changchun 130021, China. Electronic address: zhangling3@jlu.edu.cn.
PMID: 40216264 DOI: 10.1016/j.bcp.2025.116926
Abstract

Breast Cancer (BC) is the most common malignant tumor among women. There is a pressing demand to develop new therapeutic strategies for advanced BC. In this report, we investigated whether Transglutaminase 2 (TGM2) is involved in BC growth. Moreover, a high expression of TGM2 in BC was found to be correlated with a poor prognosis. Thus, TGM2 might be a prospective therapeutic target in BC. We examined if a small molecule inhibitor of TGM2, GK921, could suppress BC growth. GK921 inhibited TGM2 activity and induced autophagy-dependent cell death in BC cell lines. Additionally, we found that GK921 increased p53 levels, which decreased the expression of mTOR, a classical upstream regulator of Autophagy. Finally, we found that down regulation of TGM2 using RNAi activated Autophagy. Consistent with these findings, GK921 significantly suppressed breast tumor growth in mouse models, suggesting that TGM2 may be a potential therapeutic target for BC treatment.

Keywords

Autophagy; Breast cancer; Cell death; Tumor growth.

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