ZDHHC22-mediated mTOR palmitoylation restrains breast cancer growth and endocrine therapy resistance

作者全名："Huang, Jiefeng; Li, Jie; Tang, Jun; Wu, Yushen; Dai, Fengsheng; Yi, Ziying; Wang, Yan; Li, Yunhai; Wu, Yue; Ren, Guosheng; Xiang, Tingxiu"

作者地址："[Huang, Jiefeng] Jinan Univ, Clin Med Coll 2, Shenzhen Peoples Hosp, Dept Breast & Thyroid Surg, Shenzhen 518020, Guangdong, Peoples R China; [Huang, Jiefeng; Li, Jie] Southern Univ Sci & Technol, Affiliated Hosp 1, Shenzhen 518020, Guangdong, Peoples R China; [Huang, Jiefeng] Shenzhen Peoples Hosp, Dept Gen Surg, Shenzhen 518020, Guangdong, Peoples R China; [Li, Jie] Jinan Univ, Shenzhen Peoples Hosp, Dept Dermatol, Clin Med Coll 2, Shenzhen 518020, Guangdong, Peoples R China; [Huang, Jiefeng; Li, Jie; Tang, Jun; Wu, Yushen; Dai, Fengsheng; Yi, Ziying; Wang, Yan; Li, Yunhai; Wu, Yue; Ren, Guosheng] Chongqing Med Univ, Chongqing Key Lab Mol Oncol & Epigenet, Affiliated Hosp 1, Chongqing 400016, Peoples R China; [Wu, Yushen; Yi, Ziying; Li, Yunhai; Ren, Guosheng] Chongqing Med Univ, Affiliated Hosp 1, Dept Endocrine & Breast Surg, Chongqing 400016, Peoples R China; [Xiang, Tingxiu] Chongqing Univ Canc Hosp, Chongqing Key Lab Translat Res Canc Metastasis &, Chongqing 400030, Peoples R China"

通信作者："Ren, GS (通讯作者)，Chongqing Med Univ, Chongqing Key Lab Mol Oncol & Epigenet, Affiliated Hosp 1, Chongqing 400016, Peoples R China.; Ren, GS (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Dept Endocrine & Breast Surg, Chongqing 400016, Peoples R China.; Xiang, TX (通讯作者)，Chongqing Univ Canc Hosp, Chongqing Key Lab Translat Res Canc Metastasis &, Chongqing 400030, Peoples R China."

来源：INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES

ESI学科分类：BIOLOGY & BIOCHEMISTRY

WOS号：WOS:000785015100003

JCR分区：Q1

影响因子：9.2

年份：2022

卷号：18

期号：7

开始页：2833

结束页：2850

文献类型：Article

关键词：Breast cancer; ZDHHC22; Palmitoylation; mTOR; Endocrine therapy resistance

摘要："Palmitoylation is essential for the classic hallmarks of cancers through regulating protein stability and protein-protein interactions. ZDHHC22, as a well-known member of palmitoyltrans-ferase family, its role has not been revealed in cancer. We found ZDHHC22 expression was significantly lower in estrogen receptor (ER) negative breast cancer (BrCa) tissues and cell lines, and its expression was positively corelated with the clinical prognosis of BrCa patients. The lower expression of ZDHHC22 might be caused by its promoter methylation. ZDHHC22 inhibited the proliferation capability of BrCa cells both in vitro and in vivo, depending on its encoding palmitoyltransferase activity. In terms of the mechanisms, ZDHHC22 reduced mTOR stability via palmitoylation and decreased the activation of the AKT signaling pathway. Furthermore, ectopic expression of ZDHHC22 could restore the sensitivity to tamoxifen therapy in MCF-7R cells. Collectively, ZDHHC22 may serve as a prognostic biomarker and therapeutic target, providing the theoretical foundation for exploring specific palmitoylation drugs targeted, especially for endocrine therapy-resistant BrCa patients."

基金机构："National Natural Science Foundation of China [82172619, 31420103915]; Natural Science Foundation of Chongqing [CSTC2021jscx-gksb-N0023, 2019ZX002]; Shenzhen Key Medical Discipline Construction Fund [SZXK015]"

基金资助正文："We thank Dr. Lin, from Shantou Affiliated Hospital of Sun Yat-Sen University for providing the tamoxifen-resistant MCF-7 (MCF-7R) and MCF-7 breast cancer cell. This study was supported by grants from the National Natural Science Foundation of China (No.82172619, 31420103915), the Natural Science Foundation of Chongqing (CSTC2021jscx-gksb-N0023,2019ZX002) and Shenzhen Key Medical Discipline Construction Fund (No. SZXK015)."