The dynamic role of nucleoprotein SHCBP1 in the cancer cell cycle and its potential as a synergistic target for DNA-damaging agents in cancer therapy

• DOI: 10.1186/s12964-024-01513-0
• Publication Date: 2024-02-16T18:02:36Z
• Authors: Mei Zhou; Limin Duan; Jiangbin Chen; Yumei Li; Zhengrong Yin; Siwei Song; Yaqi Cao; Ping Luo; Fan Hu; Guanghai Yang; Juanjuan Xu; Tingting Liao; Yang Jin
• Keywords: Mitotic catastrophe; CHEK1; Wee1

Abstract Background Malignant tumours seriously threaten human life and health, effective treatments for cancer are still being explored. The ability of SHC SH2 domain-binding protein 1 (SHCBP1) to induce cell cycle disturbance inhibit tumour growth has been increasingly studied, but its dynamic role in the corresponding effects leading mitotic catastrophe DNA damage have rarely studied. Results In this paper, we found that nucleoprotein SHCBP1 exhibits spatiotemporal expression during cycle, knockdown slowed progression by inducing spindle disorder, as reflected premature entry multipolar formation. This dysfunction was caused G2/M checkpoint impairment mediated downregulated WEE1 kinase NEK7 (a member mammalian NIMA-related family) upregulated centromere/kinetochore Zeste White 10 (ZW10) expression. Moreover, both vivo vitro experiments confirmed significant inhibitory on growth. Based these findings, combination with low-dose DNA-damaging agents had synergistic tumouricidal cells. response treatment, cells were forced into phase considerable unrepaired lesions, catastrophe. These attributed not only abrogation disrupted function also repair system, demonstrated mass spectrometry-based proteomic western blotting analyses. Consistently, patients low tissue more sensitive radiotherapy. However, combined tubulin-toxic drugs weakened killing effect cells, which may guide choice chemotherapeutic clinical practice. Conclusion summary, elucidated described a novel mechanism regulates through targeting increases sensitivity agent therapy, indicating potential treatment. Graphical