Abstract
Microtubule minus-end binding proteins (-TIPs) are critical regulators of microtubule dynamics and stability, whose dysfunctions are increasingly associated with tumorigenesis and cancer progression. This review systematically consolidates current research advances on the molecular characteristics, oncogenic mechanisms, and therapeutic potential of -TIPs in cancer. By integrating preclinical studies, multi-omics data, and clinical evidence, it was found that calmodulin-regulated spectrin-associated proteins (CAMSAPs) and abnormal spindle microtubule assembly (ASPM) primarily exhibit oncogenic properties, whereas CAMSAP3 acts as a tumor suppressor by negatively regulating tumor cell migration. Studies also demonstrate that pharmacological inhibition of the γ-tubulin ring complex (γ-TuRC) effectively attenuates the centrosomal hyper-clustering capacity of malignant cells, thereby suppressing invasive phenotypes. This result underscores the therapeutic value of targeting -TIPs. In summary, -TIPs play critical and complex roles in cancer progression and hold significant potential as prognostic biomarkers and therapeutic targets. Intervention strategies focusing on specific -TIPs, such as γ-TuRC, offer promising strategies for precision cancer therapy; however, the context-dependent functions of these proteins require further investigation to facilitate clinical translation.