Calcium and cancer metastasis: Discoveries from zebrafish xenografts

Cancer metastasis remains the leading cause of cancer-related deaths, highlighting the urgent need for therapies targeting metastatic processes. Dysregulated calcium (Ca²⁺) signaling is increasingly linked to metastasis and offers a promising, underexplored therapeutic target. The zebrafish xenograft model has emerged as a powerful tool for studying cancer due to its optical transparency, genetic similarity to humans, and rapid development. This review outlines how zebrafish xenografts have been employed to investigate Ca²⁺ signaling in cancer progression, revealing roles for ORAI1 in nasopharyngeal carcinoma, TRPM8 in prostate cancer, VDAC1 and TMBIM6 in breast cancer, and TRPV1 in gastric cancer. These studies highlight the zebrafish xenograft model's advantages in visualization, cost, and throughput over traditional systems. Despite its promise, the zebrafish xenograft model remains underutilized in Ca²⁺-related metastasis research. Future work using transgenic lines like tg-EGFP:flk1 and tg-GCaMP, CRISPR knockouts, morpholinos or optogenetic approaches could unlock deeper insights and guide novel metastasis-targeting therapies.