The Emerging Role of CACNA1E in Cancer: Molecular Mechanisms and Therapeutic Implications.

Voltage-gated calcium channels (VGCCs) are crucial membrane proteins that mediate calcium influx. The CACNA gene family, which encodes the alpha subunits of VGCC complexes, is essential for forming functional calcium channels and plays significant roles in various cancers. This review focuses on the CACNA1E gene, which encodes the Cav2.3 channel α1E subunit, and systematically elaborates its role in cancer. Studies have identified CACNA1E as a key prognostic stemness-related gene in bladder cancer. Its somatic mutations are associated with the development of air pollution-related lung cancer and non-small cell lung cancer. In breast cancer, genetic variations and DNA methylation differences in CACNA1E have also been reported. Functionally, CACNA1E drives tumor progression by regulating calcium signaling. For example, in osteosarcoma, METTL3-mediated m⁶A modification stabilizes CACNA1E mRNA, activating the WNT7B/Ca²⁺ signaling pathway and thereby promoting tumor progression and chemoresistance. The expression of CACNA1E is closely linked to patient prognosis, with its amplification and overexpression correlating with relapse in favorable histology Wilms' tumor. Additionally, CACNA1E is involved in therapy resistance, as evidenced by its downregulation being associated with temozolomide resistance in glioblastoma. Collectively, this evidence suggests that CACNA1E, along with other VGCC members, may serve as a potential prognostic biomarker and therapeutic target in cancer. Future research should further explore their molecular mechanisms, interactions with the tumor microenvironment, and clinical translation potential.