Ki67 is a Graded Rather than a Binary Marker of Proliferation versus Quiescence

• Published in: Cell reports (Cambridge) Vol. 24; no. 5; pp. 1105 - 1112.e5
• Main Authors: Miller, Iain, Min, Mingwei, Yang, Chen, Tian, Chengzhe, Gookin, Sara, Carter, Dylan, Spencer, Sabrina L.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 31.07.2018
• Subjects: CDK2 activity; Cell Cycle; Cell Line; Cell Proliferation; heterogeneity; Humans; Ki-67 Antigen - genetics; Ki-67 Antigen - metabolism; Ki67; MCF-7 Cells; quiescence; Single-Cell Analysis; single-cell tracking; time-lapse imaging; time-lapse imaging; quiescence; CDK2 activity; single-cell tracking; Ki67; heterogeneity
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2018.06.110

Ki67 staining is widely used as a proliferation indicator in the clinic, despite poor understanding of this protein’s function or dynamics. Here, we track Ki67 levels under endogenous control in single cells over time and find that Ki67 accumulation occurs only during S, G2, and M phases. Ki67 is degraded continuously in G1 and G0 phases, regardless of the cause of entry into G0/quiescence. Consequently, the level of Ki67 during G0 and G1 in individual cells is highly heterogeneous and depends on how long an individual cell has spent in G0. Thus, Ki67 is a graded rather than a binary marker both for cell-cycle progression and time since entry into quiescence. [Display omitted] •Ki67 levels are hard-wired into cell-cycle progression and cell-cycle exit•Ki67 is degraded continuously in G0 and G1 and accumulates from S to M phases•Ki67 levels in G0 and G1 indicate how long a cell has spent in G0/G1•This study enhances interpretation of this common clinical biomarker Ki67 is one of the most widely used markers of proliferation in oncology. Contrary to its canonical use as a binary marker of proliferation versus quiescence, Miller et al. find that Ki67 levels decay steadily in quiescent cells, which may enable more advanced clinical applications.