(1) We discuss how loss of TRAIL mediated apoptosis occurred in thyroid cancer cells and how different strategies can be used to restore apoptosis in resistant cancer cells; (2) We provide detailed account of seemingly opposite roles of NOTCH signaling in thyroid cancers; (3) TGF/SMAD mediated signaling also needs detailed research because of context dependent role in thyroid cancer.
These data indicate that nitric oxide-mediated S-nitrosylation of GAPDH and subsequent nuclear translocation of GAPDH might function as a mediator of TRAIL-induced cell death in thyroid cancer cells.
Our study demonstrated that IFNgamma combined with TRAIL can trigger apoptosis in vitro in several resistant thyroid tumor cell lines, such as thyroid anaplastic carcinoma cells (ARO cells), while either agent alone exerts only a minimal effect.
Our observations indicate that TRAIL effectively kills carcinomas that originate from the follicular epithelium of the thyroid gland, by inducing caspase-mediated apoptosis, and may provide a potentially potent therapeutic reagent against thyroid cancer.