MT1G inhibits the growth and epithelial-mesenchymal transition of gastric cancer cells by regulating the PI3K/AKT signaling pathway

Abstract

Gastric carcinoma (GC) is a malignant tumor that has high mortality and morbidity worldwide. Although many efforts have been focused on the development and progression of GC, the underlying functional regulatory mechanism of GC needs more clarification. Metallothionein 1G (MT1G) is a member of the metallothionein family (MTs), and hypermethylation of MT1G occurred in a variety of cancers, including gastric cancer. However, the functional mechanism of MT1G in GC remains unclear. Here, we demonstrated that MT1G was down-regulated in GC tissues and cells. Overexpression of MT1G inhibited cell proliferation, foci formation and cell invasion, while knockdown of MT1G increased cell proliferation, foci formation and cell invasion. In addition, MT1G overexpression inhibited cell cycle progression and MT1G deficiency exerted opposite phenotype. p-AKT was negatively regulated by MT1G. In summary, our study reveals that MT1G exerts crucial role in regulating of cell proliferation and migration of gastric cancer, providing new insights for MT1G-related pathogenesis and a basis for developing new strategies for treatment of GC.

Metallothionein Family Proteins as Regulators of Zinc Ions Synergistically Enhance the Anticancer Effect of Cannabidiol in Human Colorectal Cancer Cells

“…A DEG analysis using mRNA-seq has suggested that sorafenib can upregulate MT1G expression via the hypomethylation of its promoter region by binding and inhibiting DNA methyltransferase 1 (DNMT1) and increasing its promoter accessibility in hepatocellular carcinoma (HCC) cells, suggesting that MT1G might constitute a strategy for enhancing the anticancer effect of sorafenib [46]. MT1G can inhibit cell growth and the cell cycle through the PI3K/AKT signaling pathway in gastric cancer cells, as the overexpression of MT1G inhibits cell proliferation, foci formation, and cell invasion and negatively regulates p-AKT [34]. In vitro and in vivo experiments have confirmed that MT1F in colorectal cancer cells could decrease cell proliferation and colony formation, increase the rate of apoptosis to inhibit cell growth, and reduce xenograft tumor growth in MT1F-expressing mice [47].…”

“…MT family proteins play the main role in regulating the concentration of cytoplasmic zinc ions. Their expression levels are also regulated by zinc ions [33,34]. The expression levels of MT proteins in the two colorectal cancer cell lines were increased by zinc ion treatment according to a Western blot analysis, indicating that MT gene expression was regulated by CBD and zinc ions (Figure 7A and Supplementary Figure S3).…”

Upregulation of Metallothionein 1 G (MT1G) Negatively Regulates Ferroptosis in Clear Cell Renal Cell Carcinoma by Reducing Glutathione Consumption

“…Many studies have shown that iron-related oxidative stress can lead to lipid oxidation and GSH consumption, resulting in different types of cell death, among which ferroptosis is typical [24]. MT1G is a metallothionein responsible for metal ion homeostasis in cells [25][26][27], and GSEA showed that it was associated with GSH metabolism in ccRCC. However, the effect of MT1G on ferroptosis in ccRCC and its potential prognostic or therapeutic value have not been investigated.…”