The ZDHHC22 restores sensitivity toward tamoxifen therapy. A. GSEA analysis detached ZDHHC22 was significantly associated with Tamoxifen and endocrine therapy resistance. B. The ZDHHC22 and mTOR mRNA expression in tamoxifen-resistant breast cancer cells based on microarray datasets GSE7327, GSE21618, and GSE26459. C. The mTOR and ZDHHC22 mRNA expression in tamoxifen-resistant MCF-7 cells (MCF-7R) and parental cells (MCF-7) using the qRT-PCR assay. D. The mTOR and ZDHHC22 protein expression in MCF-7R and MCF-7 cells using WB assay. E. MCF-7 and MCF-7R cells were transfected with Vector and ZDHHC22 plasmid for 48 hours, followed by 20 μM tamoxifen treatment, respectively. Cell growth was measured with a CCK-8 assay at the indicated time. F. BT-549 and SK-BR-3 cells were transfected with Vector, ZDHHC22 and ZDHHC22-(C111A) plasmids, followed by 10 μM KU-0063794 treatment, respectively. Cell growth was measured with a CCK-8 assay at the indicated time. Data are presented as the mean ± SEM of three independent experiments. *P < 0.05. **P < 0.01. ***P < 0.001. ZDC22:ZDHHC22.