Ki-67促进癌症循环肿瘤细胞的浸润和转移
Ki-67 promotes circulating tumor cell intravasation and metastasis in breast cancer.
摘要(中文译文)
Ki-67作为一种经典的增殖标志物，是乳腺癌中关键的预后和预测生物标志物。在此，我们通过对88,208个循环肿瘤细胞（CTCs）的单细胞转录组进行图谱分析，并将其与乳腺癌小鼠模型中的原发灶和转移灶进行配对比较，发现CTCs中细胞周期基因显著富集，尤其是在CTC簇中。利用体内CRISPR筛选，我们鉴定出Ki-67是CTC血管内渗的关键调控因子，其敲除可减少转移。在机制上，Ki-67缺失并不抑制增殖，而是抑制参与维持细胞间黏附的基因，包括CD47和KLF4，从而将其表达与集体侵袭动力学联系起来。总之，通过将其与增殖标志物的角色解耦，我们的研究揭示了Ki-67作为转移能力分子驱动因素的一个意外功能。
Abstract
Ki-67, a canonical proliferation marker, represents a pivotal prognostic and predictive biomarker in breast cancer. Here, by profiling 88,208 single-cell transcriptomes of circulating tumor cells (CTCs) matched with primary and metastatic lesions in breast cancer mouse models, we uncover a striking enrichment of cell-cycle genes in CTCs, particularly in CTC clusters. Using in vivo CRISPR screens, we identify Ki-67 as an essential regulator of CTC intravasation, whose knockout reduces metastasis. Mechanistically, Ki-67 depletion does not curb proliferation but suppresses genes involved in maintaining cell-cell adhesion, including CD47 and KLF4, thereby linking its expression to collective invasion dynamics. Altogether, decoupling it from its role as a proliferation marker, our findings uncover an unexpected function of Ki-67 as a molecular driver of metastatic competence.
如何引用
AMA
Yongzhan Zhang, Jianwen Zhou, Karin Strittmatter, Yu Wei Zhang, Maria Waldmeier, Simran Asawa, et al. Ki-67 promotes circulating tumor cell intravasation and metastasis in breast cancer.. Cell reports. 2026; doi:10.1016/j.celrep.2026.117354.
APA
Yongzhan Zhang, Jianwen Zhou, Karin Strittmatter, Yu Wei Zhang, Maria Waldmeier, Simran Asawa, et al (2026). Ki-67 promotes circulating tumor cell intravasation and metastasis in breast cancer.. Cell reports. https://doi.org/10.1016/j.celrep.2026.117354
GB/T 7714
Yongzhan Zhang, Jianwen Zhou, Karin Strittmatter, Yu Wei Zhang, Maria Waldmeier, Simran Asawa, et al. Ki-67 promotes circulating tumor cell intravasation and metastasis in breast cancer.[J]. Cell reports, 2026 doi:10.1016/j.celrep.2026.117354.
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