Abstract
Sperm‑associated antigen 6 (SPAG6) belongs to the cancer/testis antigen family. It is a microtubule‑binding protein located on chromosome 10p12.2 and it plays an important role in various physiological processes, including ciliary movement, immune synapse formation and neurodevelopment. Abnormal SPAG6 expression occurs in multiple malignancies and developmental disorders; however, its underlying molecular mechanisms in tumorigenesis, tumor progression, clinical outcomes and therapeutic response have not been presented. This review provides a comprehensive overview of the physiological functions of SPAG6 and its mechanisms in disease, with a focus on its expression profile, function and association with disease progression and treatment response in hematologic malignancies (e.g., myelodysplastic syndrome, acute myeloid leukemia and B‑cell acute lymphoblastic leukemia) and solid tumors (e.g., breast cancer, lung cancer and osteosarcoma). SPAG6 promotes tumor progression and drug resistance by attenuating the cell cycle and through epigenetic modifications and remodeling of the tumor immune microenvironment. In addition, it may serve as a diagnostic and prognostic marker for various diseases as well as a therapeutic target.