In summary, our study indicates that the downregulation of ASCT2 by shRNA or miR-137 transfection with or without the inhibition of SNAT2 by the competitive small-molecule antagonist V-9302 significantly decreased the intracellular glutamine level, leading to attenuated growth and proliferation, increased apoptosis and autophagy, inactivation of the mTORC1 pathway, increased oxidative stress and an improved response to cetuximab in HNSCC (Fig. S4). Here, SLC1A5 is linked to head and neck squamous cell carcinoma.