Fig. 4: p53 loss/mutation increases the expression of TACC3 and KIFC1 via FOXM1 and renders cancer cells highly sensitive to TACC3 inhibition. | Cell Death & Differentiation

Fig. 4: p53 loss/mutation increases the expression of TACC3 and KIFC1 via FOXM1 and renders cancer cells highly sensitive to TACC3 inhibition.

From: Targeting TACC3 represents a novel vulnerability in highly aggressive breast cancers with centrosome amplification

Fig. 4

A BO-264 IC50 values in breast cancer cell lines from Fig. 1I, separated based on their p53 mutational status. B, C CA20 score (B) and TACC3 (C) expression in p53-wt vs. p53-mut breast cancer patients in METABRIC dataset. D Survival analyses in p53-mut breast cancer patients based on TACC3 expression in METABRIC dataset. E Western blot analysis of p53, TACC3 and KIFC1 in MCF-7 p53-wt vs p53−/− cells. F IF staining of α- (green) and γ- (red) tubulin in MCF-7 p53-wt vs p53−/− cells treated with 5 µM of BO-264. Scale bar = 10 µm. G Dose response curve of MCF-7 p53-wt vs p53−/− cells treated with BO-264 for 72 h. H Western blot analysis of the mitotic arrest marker, p-H3 (S10) and apoptosis marker, cleaved PARP in MCF-7 WT vs. p53−/− cells treated with 2 µM of BO-264. I, J Flow cytometry analysis of p-H3 (I) and Annexin V/PI staining (J) in cells from G. K FOXM1 mRNA expression in p53-wt vs. p53-mut breast cancer patients from METABRIC. L, M Correlation of FOXM1 mRNA with TACC3 (L) and KIFC1 (M) expression in p53-mut breast cancer patients from METABRIC. N Western blot analysis of FOXM1, KIFC1 and TACC3 in siFOXM1-transfected MDA-MB-231 and MCF-7 p53−/− cells. O Western blot analysis of p53, FOXM1, KIFC1 and TACC3 in MCF-7 p53−/− cells transfected with wt p53 ORF. P A scheme showing the predicted binding FOXM1 sites (yellow squares) and regions targeted by primers (P1-P4 for TACC3 and P1-P2 for KIFC1) on TACC3 and KIFC1 promoters. TSS Transcription start site. Q FOXM1 ChIP assay in MCF-7 p53-wt and p53−/− cells.

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