Inhibition of glutaminase suppresses the proliferation and invasion of esophageal squamous cancer cells via TGF-β/Smad and MAPK signaling pathways

Abstract Accumulating evidence indicates that through its conversion of glutamine to glutamate, glutaminase (GLS) serves as a crucial player in cell proliferation and survival of different cancers. Nonetheless, the roles and mechanisms of GLS in esophageal squamous cancer have not been elucidated. Herein, we found that kidney-type GLS was overexpressed in glutamine-dependent esophageal squamous cell carcinoma (ESCC) cells and tissues. In addition, high GLS expression levels were related to a shorter survival rate than low GLS expression levels. Furthermore, knocking down GLS diminished the proliferation, migration, and invasion of ESCC cells and promoted their apoptotic rate and epithelial mesenchymal transformation (EMT) via the TGF-β/Smad canonical pathway and the TGF-β noncanonical MAPK pathway. Overall, our study showed that GLS is a therapeutic target and diagnostic biomarker for ESCC.