Fig. 2: Inhibition of MITF overcomes palbociclib resistance by activating the senescence pathway in breast cancer cells.

a Volcano plot to display upregulated and downregulated genes in MCF-7 PR cells compared to MCF-7 cells. A change is considered significant if the p-value is <0.05 and the change is >2-fold. b Cell lysates from MCF-7 and MCF-7 PR cells were immunoblotted for indicated proteins. (n = 3 independent experiments). c Cell viability was examined in MCF-7 PR and T-47D PR cells treated with increasing concentration of palbociclib for 3 days after MITF depletion by shRNA (n = 3 independent experiments). d MCF-7 PR cells transfected with shScr or shMITF were treated with palbociclib, followed by immunoblotting for indicated proteins. (n = 3 independent experiments). e, f Representative images (e) and growth curves (f) of MCF-7 PR xenograft tumors with indicated treatment for 3 weeks. n = 6 mice/group. g GSEA profiling to show the enrichment of the SASP geneset in MCF7 PR cells treated with shScr or shMITF. NES score and p values were determined by GSEA software. h Heatmap profiling of SASP-associated factors in MCF-7 PR cell treated with shScr or shMITF. The displayed SASP-associated factors were selected from the top list of genes based on expression fold change. i MCF7 PR cells treated as indicated were harvested and then subjected to qPCR to examine the expression of SASP-associated factors shown in h (n = 3 independent experiments). j, k Representative images of SA-β-gal staining in MCF-7 PR cells treated with ML-329 (j) or shRNAs (k) (n = 3 independent experiments). The scale bar represents 20 μm. **p ≤ 0.01, *p ≤ 0.05. All error bars are expressed as mean ± SEM. Two-tailed Student’s t tests were employed for statistical evaluation. Source data are provided as a Source Data file.