Glutaminase promotes the malignant progression of esophageal squamous cell carcinoma via TGF-β canonical and noncanonical pathways

Accumulating evidence indicates that glutaminase (GLS) serves as a crucial player in cell proliferation and survival of cancers. Nonetheless, the roles and mechanisms of GLS in esophageal squamous cell carcinoma (ESCC) have not been elucidated. Herein, we found that GLS was over-expressed in glutamine-dependent ESCC cells and ESCC tissues. Patients with high GLS expression had a worse prognosis than those with low GLS expression. In ESCC cells, GLS knockdown inhibited the proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) of ESCC cells and promoted apoptosis. RNA-Seq analysis combined with immunoblotting showed that GLS knockdown reduced the TGF-β, p-Smad2/3, p-p38MAPK, p-ERK1/2, and p-MEK1/2 proteins, increased ROS and glutamine levels in both KYSE30 and KYSE150 cells. Overall, our study showed that GLS promoted the malignant progression via the TGF-β signaling pathway, suggesting that GLS can be a potential therapeutic target and diagnostic biomarker for ESCC.