TNF and neoplasm: Notably, exogenous stimuli such as hyperosmotic stress can also initiate endogenous TNF production in cancer cells,26 mediated through binding of the transcription factor NFAT5 to the TNF promoter.25 Hypertonicity-induced TNF release from cancer cells (and potentially also from cells in the tumor environment) could therefore substitute for lacking SM-induced TNF production, while still relying on the TNF-sensitizing activity of SM.