Fig. 3

The signaling pathways that are activated by TMEM16A in cancer. TMEM16A directly interacts with EGFR [81], and promotes EGFR phosphorylation, which activates the AKT/SRC/ERK1/2 signaling [42]. In addition, TMEM16A increases autocrine secretion of EGF in breast cancer cells [42]. TMEM16A directly interacts with IP₃R, and increased Ca²⁺ release from the ER [85]. TMEM16A activates CaMKII by increasing intracellular Ca²⁺ concentrations, and CaMKII subsequently activates the AKT/SRC/ERK1/2 signaling [42]. TMEM16A also activates the Ras-Raf-Mek-ERK1/2 signaling pathway in UM-SCC1 HNSCC cells and T24 bladder cells [44]. In SMMC-7721 human hepatoma cells, TMEM16A activates the p38 signaling pathway [52]. TMEM16A activates the NFκB signaling pathway and promotes the gene transcription in glioma cells [56]. +, activates the signaling pathway.?, the mechanisms of how TMEM16A activates the signaling pathway are unknown