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

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.