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  3. TUFT1 regulates cancer progression by suppressing centrosome amplification and mitotic spindle multipolarity

TUFT1 regulates cancer progression by suppressing centrosome amplification and mitotic spindle multipolarity

  • Cell Death Dis. 2025 Sep 29;16(1):673. doi: 10.1038/s41419-025-08010-3.
Shaojie Feng # 1 2,  Mengmeng Zhao # 2,  Donghui Zhang # 3,  Yan Zhang 1,  Lingyuan Min 2,  Xianqiang Liu 4,  Huan Shi 5,  Tianning Wang 6 7
Affiliations

Affiliations

  • 1 Breast Disease Diagnosis and Treatment Center/Department of Thyroid Surgery, Central Hospital Affiliated to Shandong First Medical University, Jinan, China.
  • 2 Research Center of Translational Medicine, Central Hospital Affiliated to Shandong First Medical University, Jinan, China.
  • 3 Zhanjiang Institute of Clinical Medicine, Central People's Hospital of Zhanjiang, Guangdong Medical University Zhanjiang Central Hospital, Zhanjiang, China.
  • 4 Breast Disease Diagnosis and Treatment Center/Department of Thyroid Surgery, Central Hospital Affiliated to Shandong First Medical University, Jinan, China. arthur730318@126.com.
  • 5 Department of Internal Medicine-Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China. 15553119187@163.com.
  • 6 Breast Disease Diagnosis and Treatment Center/Department of Thyroid Surgery, Central Hospital Affiliated to Shandong First Medical University, Jinan, China. wangtianning@pku.edu.cn.
  • 7 Research Center of Translational Medicine, Central Hospital Affiliated to Shandong First Medical University, Jinan, China. wangtianning@pku.edu.cn.
  • # Contributed equally.
PMID: 41022752 DOI: 10.1038/s41419-025-08010-3
Abstract

Centrosome amplification (CA) has been observed in various solid tumors and contributes to chromosomal instability (CIN) and poor clinical prognosis in patients with Cancer. CA also inhibits cell proliferation by inducing cell-cycle arrest and cell death. However, the mechanism of regulation of centrosome number in Cancer cells and its effect on CIN and cell proliferation remains elusive. Here, we report that tuftelin (TUFT1) is a novel centrosomal protein that localizes to the proximal ends of parent centrioles. TUFT1 prevents CA and mitotic spindle multipolarity by suppressing premature polo-like kinase 1 activation. In addition, TUFT1 is phosphorylated by NIMA-related kinase 2 (NEK2), and the phosphorylation status of TUFT1 is essential for coordinating centrosome number and cell proliferation in cervical and breast cancers. Data from clinical breast Cancer samples indicate that the combined detection of TUFT1 and NEK2 expression reflects tumor malignancy and patient survival with higher precision. Overall, these results reveal a crucial role of TUFT1 in the regulation of tumor progression through centrosome number control. Thus, TUFT1 represents a promising target for diagnostic and therapeutic approaches for cancers.

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