Figure 2.

Distribution of ANO1/TMEM16A in different tissues and its role in diseases. (A) In epithelial cells, ANO1 activation contributes to electrolyte and music secretion. Activation of GPCRs causes an increase in intracellular cAMP and Ca²⁺, further inducing Cl⁻ secretion through the activation of CFTR and ANO1. A crosstalk between CFTR and ANO1-dependent secretions also occurs for regulation of secretory signaling in the airway epithelia. ANO1 high expression or hyperactivity can cause inflammatory diseases such as asthma and diarrhea. (B) Outward flow of Cl⁻ through the activation of ANO1 in smooth muscle cells causes depolarization and smooth muscle contraction. ANO1 high expression or hyperactivity is responsible for asthma diarrhea, and hypertension. (C) In DRG sensory neurons, activation of ANO1 by intracellular Ca²⁺ or heat causes Cl⁻ efflux and increases neuronal excitability for induction of neuropathic pain. The functional coupling between TRPV1 and ANO1 is also involved in nociception. (D) In cancer cells, ANO1 upregulation promotes cell proliferation and migration, whereas ANO1 downregulation induces apoptosis through multiple signaling pathways, including EGFR/MAPK signaling pathway⁹⁸, CaMKII/MAPK signaling pathway⁵¹, TGF-β signaling pathway¹²⁰ and NF-κB signaling pathway¹²¹. Pharmacological activation of ANO1 by activators or potentiators may serve as a therapeutic strategy for treatment of CF, dry mouth and dry eye syndromes, and inhibition of ANO1 by inhibitors may be beneficial for ANO1 related channelopathies including asthma, diarrhea, hypertension, neuropathic pain and cancers.