Multiple roles of ANO6 in tumors, molecular mechanism and its potential therapeutic value

Anoctamin 6 (ANO6/TMEM16F) is a calcium-activated ion channel and phospholipid disruptor that plays a key role in maintaining cellular homeostasis. This review focuses on the role of ANO6 in various cancers. On one hand, ANO6 is highly expressed in pancreatic cancer, gastric cancer, and glioma, while its expression is downregulated in breast cancer, prostate cancer, cervical cancer, and ovarian cancer. This indicates its functional diversity across different cancer types, reflecting the complex regulatory mechanisms of ANO6 in the tumor microenvironment. In pancreatic cancer, ANO6 is highly expressed, and it promotes pancreatic cancer metastasis through the ERK signaling pathway. In melanoma, ANO6 is closely associated with poor patient prognosis, clinical-pathological characteristics, tumor immunity, and tumor heterogeneity. In breast cancer, ANO6 is a ferroptosis gene associated with prognosis, and its low expression is linked to poor outcomes, making it a key independent predictor of overall survival in breast cancer patients. Additionally, the relationship between ANO6 and immune cells highlights its potential role in cancer immune surveillance and therapy. Finally, we found that ANO6 may regulate immune cell exhaustion in the tumor microenvironment by influencing macrophage polarization and T cell recruitment and activation. This review highlights the diverse roles of ANO6 in different cancers and its potential as a diagnostic and therapeutic tool. Future studies should address the mechanistic details of ANO6 involvement in cancer, validate its clinical utility, and explore its therapeutic potential in combination with existing therapies.