2. Academic Validation
  3. Niclosamide suppresses gastric cancer progression through YTHDF2 inhibition-affected lactate metabolic reprogramming

Niclosamide suppresses gastric cancer progression through YTHDF2 inhibition-affected lactate metabolic reprogramming

  • iScience. 2025 Oct 27;28(11):113868. doi: 10.1016/j.isci.2025.113868.
Mosheng Tang 1,  Yiyin Hu 2,  Xiaohui Zhu 2,  Jichen Dai 3,  Rui Li 4,  Xinran Feng 2,  Kangrui Chi 2,  Xinyi Li 4,  Qiaofei Zhang 4,  Ke Chen 4,  Ruoying Cao 2,  Hanqing Zhu 2,  Haoran Huang 5,  Haipeng Wu 4,  Lejia Sun 4,  Tongke Chen 6,  Jun Wu 7,  Huafu Wang 8,  Zhihong Gui 9
Affiliations

Affiliations

  • 1 Radiotherapy Center, Lishui People's Hospital, 15 Dazhong Road, Liandu District, Lishui 323000, Zhejiang, China.
  • 2 The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, Zhejiang, China.
  • 3 Department of Head and Neck Surgery, Renji Hospital, Shanghai Jiaotong University, Shanghai 200240, China.
  • 4 Wenzhou Medical University, Wenzhou 325027, Zhejiang, China.
  • 5 School of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou 325000, Zhejiang, China.
  • 6 Laboratory Animal Centre, Wenzhou Medical University, Wenzhou 325000, Zhejiang, China.
  • 7 Department of Pathology, Lishui People's Hospital, Lishui 323000, Zhejiang, China.
  • 8 Department of Pharmac, Lishui People's Hospital, Lishui 323000, Zhejiang, China.
  • 9 Department of Nephrology, Lishui People's Hospital, Lishui 323000, Zhejiang, China.
PMID: 41323282 DOI: 10.1016/j.isci.2025.113868
Abstract

Gastric Cancer (GC), a highly aggressive tumor with significant mortality, exhibits metabolic reprogramming involving glucose, lipid, and amino acid metabolism. This study employed non-targeted metabolomics and transcriptomics to analyze metabolic alterations in patients with GC, complemented by single-cell RNA-seq to dissect lactate shuttle dynamics and metabolic alterations between tumor epithelial and endothelial cells. The impact of niclosamide and YTHDF2, an m6A methylation regulator, on gastric Cancer cell proliferation was investigated both in vitro and in vivo. Niclosamide disrupted metabolic reprogramming and lactate dynamics within the tumor microenvironment. YTHDF2 emerged as a critical modulator of GC metabolism, with niclosamide suppressing tumors through the YTHDF2-mediated regulation of metabolic genes. Our research revealed comprehensive metabolic alterations in gastric Cancer, including upregulated lactate metabolism that promotes tumorigenesis via the lactate shuttle. Niclosamide targets the m6A methylation regulatory protein YTHDF2, which influences genes related to metabolism, indicating its potential as a prospective treatment for GC.

Keywords

cancer; molecular physiology; pharmacology.

Figures
Products