2. Academic Validation
  3. MT1H inhibits the growth of gastric cancer by regulating SLC6A19/TTC39B/ADM2 and activating p53-dependent autophagy

MT1H inhibits the growth of gastric cancer by regulating SLC6A19/TTC39B/ADM2 and activating p53-dependent autophagy

  • Sci Rep. 2025 Mar 18;15(1):9339. doi: 10.1038/s41598-025-91319-y.
Yamin Xing # 1 2,  Guangyuan Li # 1 2,  Ganggang Li 2,  Jixuan Xu 3,  Ting Zhang 2,  Mengxue Li 1,  Chunxiao Gao 1 2,  Miaoran Fu 4,  Pengyuan Zheng 5,  Xiufeng Chu 6 7
Affiliations

Affiliations

  • 1 Marshall B. J. Medical Research Center, Zhengzhou University, Zhengzhou, 450052, Henan, China.
  • 2 Department of Oncology, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
  • 3 Department of Gastrointestinal & Thyroid Surgery, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
  • 4 Department of Neurology, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
  • 5 Marshall B. J. Medical Research Center, Zhengzhou University, Zhengzhou, 450052, Henan, China. pyzheng@zzu.edu.cn.
  • 6 Marshall B. J. Medical Research Center, Zhengzhou University, Zhengzhou, 450052, Henan, China. Chuxiufeng831031@gmail.com.
  • 7 Department of Oncology, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, China. Chuxiufeng831031@gmail.com.
  • # Contributed equally.
PMID: 40102553 DOI: 10.1038/s41598-025-91319-y
Abstract

Metallothioneins (MTs) are a class of cysteine-rich proteins that actively participate in the cellular defense against free radicals. However, owing to the high heterogeneity among different MTs, comprehensive investigations are needed to determine the biological activities and distribution patterns of each MT in different tissues. In the present study, ectopic expression of MT1H significantly inhibited the proliferation of gastric Cancer cells. Mechanistically, MT1H was transported into the nucleus and regulated the expression of key genes involved in nutrient transportation and homeostasis, such as SLC6A19, TTC39B, and ADM2, and thereby activating the p53 and Autophagy pathways. Additionally, survival analysis of data from the TCGA and Other databases revealed that gastric Cancer patients with high expression of MT1H had longer survival. Furthermore, MT1H was undetectable in most gastric cell lines, but its expression was increased upon treatment with dexamethasone (Dexa) and the metal ion zinc. Therefore, MT1H emerges as a valuable tumor suppressor, a biomarker for the prognosis, and a promising therapeutic target in gastric Cancer patients.

Keywords

Autophagy; Gastric cancer; Metallothionein; p53.

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