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. Author manuscript; available in PMC: 2021 Sep 9.
Published in final edited form as: Nature. 2020 Sep 9;585(7825):447–452. doi: 10.1038/s41586-020-2690-1

Figure 1. PLK4 inhibition is synthetic lethal with TRIM37 amplification.

Figure 1.

(A) Fold increase in cell number after centrinone (125 nM) addition. n = 3, biological replicates. Mean ± s.e.m.

(B) Immunoblot showing TRIM37 protein levels in WT and TP53−/− MCF-7 cells stably expressing a control or one of two independent TRIM37-targeting shRNAs. β-Actin, loading control. Representative data; n = 3, biological replicates. For gel source data, see Supplementary Figure 1.

(C) Representative data of a 10 day clonogenic survival of indicated MCF-7 cell lines treated with DMSO (control) or centrinone (PLK4i, 125 nM).

(D) Quantification of (C), n = 3, biological replicates. P values, unpaired two-tailed t-test. Mean ± s.e.m.

(E) MCF-7 cells treated with DMSO (control) or centrinone (PLK4i, 125 nM) were analysed for DNA content, and stained for senescence-associated β-galactosidase expression. Representative data of n = 3, biological replicates. Scale bars, 100 μm.

(F) Percentage of sub-G1 cells from (E). n = 3, biological replicates. P values, unpaired two-tailed t-test. Mean ± s.e.m.

(G) Quantification of the percentage of SA-β-gal positive cells from (E). n = 3, biological replicates, each comprising ≥ 200 cells. P values, unpaired two-tailed t-test. Mean ± s.e.m.

biological replicates. P values, paired two-tailed t-test. Mean ± s.e.m. AS, analogue sensitive.

(H) Quantification of clonogenic survival data for 17q23-amplified and non-17q23-amplified breast cancer cells transduced with a TRIM37-shRNA or vector control and treated with DMSO (control) or centrinone (PLK4i, 125 nM). n = 3 biological replicates. P values, unpaired two-tailed t-test. Mean ± s.e.m.