The activation of adenosine monophosphate–activated protein kinase inhibits the migration of tongue squamous cell carcinoma cells by targeting Claudin‐1 via epithelial–mesenchymal transition

Background The role of Claudin‐1 in tongue squamous cell carcinoma (TSCC) metastasis needs further clarification, particularly its impact on cell migration. Herein, our study aims to investigate the role of Claudin‐1 in TSCC cell migration and its underlying mechanisms. Methods 36 TSCC tissue samples underwent immunohistochemical staining for Claudin‐1. Western blotting and immunofluorescence analyses were conducted to evaluate Claudin‐1 expression and distribution in TSCC cells. Claudin‐1 knockdown cell lines were established using short hairpin RNA transfection. Migration effects were assessed through wound healing assays. Furthermore, the expression of EMT‐associated molecules was measured via western blotting. Results Claudin‐1 expression decreased as TSCC malignancy increased. Adenosine monophosphate–activated protein kinase (AMPK) activation led to increased Claudin‐1 expression and membrane translocation, inhibiting TSCC cell migration and epithelial–mesenchymal transition (EMT). Conversely, Claudin‐1 knockdown reversed these inhibitory effects on migration and EMT caused by AMPK activation. Conclusions Our results indicated that AMPK activation suppresses TSCC cell migration by targeting Claudin‐1 and EMT pathways. Schematic diagram of the potential antitumor mechanism of adenosine monophosphate–activated protein kinase (AMPK) in tongue squamous cell carcinoma (TSCC) cells. The activation of AMPK by 5‐aminoimidazole‐4‐carboxamide1‐β‐D‐ribofuranoside (AICAR) increased Claudin‐1 expression, induced its membrane translocation, and inhibited the EMT and migration of TSCC cells. Moreover, the knockdown of Claudin‐1 reversed the inhibitory effects of AMPK on EMT and migration. This cascade of events implies that the possible mechanism of the inhibitory effects of AMPK on the migration of tongue squamous cell carcinoma TSCC cells was mediated by Claudin‐1 via the suppression of EMT.