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Microtubule Minus-End Binding Proteins in Cancer: Advances
Qingwen Wang1, Xiuling Li1, Meng Xie1
1Department of Gastroenterology, Zhengzhou University People's Hospital, Henan Provincial People's Hospital, Zhengzhou 450003, China.
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.
Insights
Microtubule minus-end binding proteins (-TIPs) are key in cancer. Targeting specific -TIPs, like the γ-tubulin ring complex (γ-TuRC), shows promise for precision cancer therapy.
Area of Science:
- Oncology
- Cell Biology
- Molecular Biology
Background:
- Microtubule minus-end binding proteins (-TIPs) regulate microtubule dynamics and stability.
- -TIP dysfunctions are linked to tumorigenesis and cancer progression.
Purpose of the Study:
- To review research on -TIPs' molecular characteristics, oncogenic mechanisms, and therapeutic potential in cancer.
- To explore the role of specific -TIPs and their targeting for cancer therapy.
Main Methods:
- Systematic review integrating preclinical studies, multi-omics data, and clinical evidence.
- Analysis of oncogenic and tumor-suppressive roles of specific -TIPs (CAMSAPs, ASPM).
- Evaluation of pharmacological inhibition of the γ-tubulin ring complex (γ-TuRC).
Main Results:
- Calmodulin-regulated spectrin-associated proteins (CAMSAPs) and abnormal spindle microtubule assembly (ASPM) show oncogenic properties.
- CAMSAP3 acts as a tumor suppressor by inhibiting tumor cell migration.
- Inhibiting γ-TuRC reduces malignant cell centrosomal hyper-clustering and suppresses invasion.
Conclusions:
- -TIPs have complex roles in cancer progression, serving as potential biomarkers and therapeutic targets.
- Targeting specific -TIPs, like γ-TuRC, offers a promising strategy for precision cancer therapy.
- Further research is needed to understand context-dependent functions for clinical translation.
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