Fig. 7.

WDR5 inhibitor sensitizes breast cancer cells to paclitaxel. a One TN (MBC2) and one LB (MBC26) PDXs were treated for 3 days with diverse concentrations of paclitaxel (PTX) (1 nM, 5 nM, and 10 nM) alone or in combination with OICR-9429 (20 μM) or galunisertib (10 μM). Cell viability is reported as ratio of the control group (vehicle). Differences among indicated concentrations were calculated by applying a Student t test (mean ± SD of n = 3 experiments; *P < 0.05; **P < 0.01). Asterisk colors are associated with corresponding treatment. b MDA-MB-231 cells were treated for 3 days with PTX (10 nM) upon OICR-9429 (20 μM) or galunisertib (10 μM) treatments. Cell viability of each condition was expressed as ratio to the control group (vehicle) and significant differences among groups calculated by an unpaired Student t test (mean ± SD of n = 3 biological replicas; ***P < 0.001). c MDA-MB-231 cells were treated as above and analyzed by flow cytometry for bromodeoxyhuridine (BrDU) and propidium iodide (PI) content. Percentage (%) of cell population in each phase of cell cycle (G0/G1, S, S-not cycling and G2/M) is represented for each condition. Statistical significance was calculated by applying two-way ANOVA followed by the Bonferroni post test for multiple comparisons (*P < 0.05; **P < 0.01; ***P < 0.001). Colors of the asterisks are associated with the phase of the cell cycle in which the differences were detected. d Schematic representation of WDR5 mechanism of action in breast cancer for the maintenance of cells hovering from mesenchymal to epithelial-like phenotype. TGFβ1 is directly regulated by WDR5 and largely participates to this governance so effectively that inhibition of WDR5-TGFβ1 axis switches cell state from metastable to low metastatic and reduces breast cancer progression