Ndc80-KO Mouse

Ndc80, a key component of the kinetochore-microtubule attachment machinery in eukaryotic cells, is essential for successful mitotic cell division [1,3,4,6,7]. The Ndc80 complex, with a small disordered region in the Hec1 subunit (the N-terminal "tail" domain), mediates the formation of correct attachments between chromosomes and spindle microtubules [1]. These attachments need to be stable yet regulated for timely, error-free mitotic progression. The complex is also involved in pathways like chromosome segregation and spindle checkpoint signaling [3,6,7].

In triple-negative breast cancer (TNBC), Ndc80 is considered a cisplatin-resistant gene. Its expression is upregulated in cisplatin-resistant cells and TNBC tissues compared to normal tissues. Overexpression of Ndc80 promotes TNBC cell viability, proliferation, and cisplatin resistance [2]. In glioma, the Hec1 component of the Ndc80 complex is overexpressed, indicating poor prognosis. It promotes cell proliferation, DNA replication and repair, and macrophage polarization from M1 to M2 phenotype, contributing to an immunosuppressive tumor microenvironment [5].

In conclusion, Ndc80 is crucial for mitotic cell division through its role in kinetochore-microtubule attachments. Studies in TNBC and glioma suggest its potential as a therapeutic target. Understanding Ndc80's function helps in unravelling the mechanisms of cancer drug resistance and tumor progression, providing new directions for cancer treatment [2,5].

References:

1. Wimbish, Robert T, DeLuca, Jennifer G. 2020. Hec1/Ndc80 Tail Domain Function at the Kinetochore-Microtubule Interface. In Frontiers in cell and developmental biology, 8, 43. doi:10.3389/fcell.2020.00043. https://pubmed.ncbi.nlm.nih.gov/32161753/

2. Li, Jing, Xu, Xiaoqin, Peng, Xiting. 2022. NDC80 Enhances Cisplatin-resistance in Triple-negative Breast Cancer. In Archives of medical research, 53, 378-387. doi:10.1016/j.arcmed.2022.03.003. https://pubmed.ncbi.nlm.nih.gov/35346500/

3. Chen, Jingxun, Ünal, Elçin. 2021. Meiotic regulation of the Ndc80 complex composition and function. In Current genetics, 67, 511-518. doi:10.1007/s00294-021-01174-3. https://pubmed.ncbi.nlm.nih.gov/33745061/

4. Ustinov, N B, Korshunova, A V, Gudimchuk, N B. . Protein Complex NDC80: Properties, Functions, and Possible Role in Pathophysiology of Cell Division. In Biochemistry. Biokhimiia, 85, 448-462. doi:10.1134/S0006297920040057. https://pubmed.ncbi.nlm.nih.gov/32569552/

5. Ye, Weijie, Liang, Xisong, Chen, Ge, Cheng, Quan, Chen, Xiaoping. . NDC80/HEC1 promotes macrophage polarization and predicts glioma prognosis via single-cell RNA-seq and in vitro experiment. In CNS neuroscience & therapeutics, 30, e14850. doi:10.1111/cns.14850. https://pubmed.ncbi.nlm.nih.gov/39021287/

6. Tooley, John, Stukenberg, P Todd. . The Ndc80 complex: integrating the kinetochore's many movements. In Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology, 19, 377-91. doi:10.1007/s10577-010-9180-5. https://pubmed.ncbi.nlm.nih.gov/21311965/

7. Ciferri, Claudio, Musacchio, Andrea, Petrovic, Arsen. 2007. The Ndc80 complex: hub of kinetochore activity. In FEBS letters, 581, 2862-9. doi:. https://pubmed.ncbi.nlm.nih.gov/17521635/