PTC124 Rescues Nonsense Mutation of Two Tumor Suppressor Genes and to Repress HNSCC Cell Proliferation.

(1) Background: PTC124 (Ataluren) is an investigational drug for the treatment of nonsense mutation-mediated genetic diseases. With the exception of the tumor suppressor gene, there has been little research on cancers with nonsense mutation. By conducting a database search, we found that another two tumor suppressor genes, and , have a high nonsense mutation rate in head and neck squamous cell carcinoma (HNSCC). PTC124 may re-express the functional or in nonsense mutation or in HSNCC (2) Methods: DOK (with Y550X) or HO-1-u-1 (with E378X) HNSCC cells were treated with PTC124, and the or expression, cell viability, and - or -related downstream gene profiles were assayed. (3) Results: PTC124 was able to induce or expression in DOK and HO-1-u-1 cells. PTC124 was able to upregulate downstream genes , , and in DOK cells. PTC124 enhanced DDIT4, which is under the control of the -YAP1 pathway, in HO-1-u-1 cells. FLI-06 (a NOTCH signaling inhibitor) reversed PTC124-mediated cell growth inhibition in DOK cells. PTC124 could reverse TT-10 (a YAP signaling activator)-mediated HO-1-u-1 cell proliferation. (4) Conclusions: PTC124 can rescue nonsense mutation of and to repress HNSCC cell proliferation.