Fig. 7: Elevated CDK4 and filamin A lead to increased tubulin acetylation and stabilization, enhancing the effect of paclitaxel on mitotic aberrations.

A Acetylated tubulin (i.e., stabilized microtubules) in parental, MDA-MB-231 CDK4 and MDA-MB-231 FLNA cells, untreated or in response to 5 nM paclitaxel. Samples derived from the same experiment and blots were processed in parallel. On the right-hand side, a bar chart showing the quantification of acetylated tubulin normalized to total tubulin in the different experimental conditions is shown. The quantification is the result of averaging three experimental replicates. Data are presented as the mean±SEM, n = 3 independent experiments; two-sided unpaired t-test. B Reversion of increased tubulin acetylation in MDA-MB-231 CDK4 cells by filamin A knockdown. Samples derived from the same experiment and blots were processed in parallel. C Evaluation of abnormal cell divisions, including metaphases and anaphases, in parental, CDK4 and FLNA MDA-MB-231 variants. Cells were exposed to 5 nM paclitaxel for 4 h, washed, and allowed to recover for 48 h. At this point, the percentages of normal metaphases/anaphases, multipolar metaphases, metaphases with misaligned chromosomes, metaphases with abnormal mitotic spindles, anaphases bridges, and anaphases with lagging chromosomes were quantified in each cell line. Data are presented as the mean ± SEM, n = 3 independent experiments. Supplementary Data 4 shows the percentage of cells displaying each aberration in either baseline or treated parental, CDK4 or FLNA MDA-MB-231 variants. The pictures on the right-hand side depict examples of each mitotic aberration type. Scale bars: 10 µm. D Same as in (C) regarding abnormal nuclei resulting from the previous aberrant processes. Scale bars: 25 µm. Source data are provided as a Source data file.