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

Huang, Jiefeng1,2,3,5; Li, Jie2,4,5; Tang, Jun5; Wu, Yushen5,6; Dai, Fengsheng5; Yi, Ziying5,6; Wang, Yan5; Li, Yunhai5,6; Wu, Yue5; Ren, Guosheng5,6; Xiang, Tingxiu7

2022

10.7150/ijbs.70544

International Journal of Biological Sciences   影响因子和分区

1449-2288

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.

Breast cancer ZDHHC22 Palmitoylation mTOR Endocrine therapy resistance

SCI

英语

其他

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

Biochemistry & Molecular Biology ; Life Sciences & Biomedicine - Other Topics

Biochemistry & Molecular Biology ; Biology

WOS:000785015100003

IVYSPRING INT PUBL

Web of Science

1.Jinan Univ, Clin Med Coll 2, Shenzhen Peoples Hosp, Dept Breast & Thyroid Surg, Shenzhen 518020, Guangdong, Peoples R China
2.Southern Univ Sci & Technol, Affiliated Hosp 1, Shenzhen 518020, Guangdong, Peoples R China
3.Shenzhen Peoples Hosp, Dept Gen Surg, Shenzhen 518020, Guangdong, Peoples R China
4.Jinan Univ, Shenzhen Peoples Hosp, Dept Dermatol, Clin Med Coll 2, Shenzhen 518020, Guangdong, Peoples R China
5.Chongqing Med Univ, Chongqing Key Lab Mol Oncol & Epigenet, Affiliated Hosp 1, Chongqing 400016, Peoples R China
6.Chongqing Med Univ, Affiliated Hosp 1, Dept Endocrine & Breast Surg, Chongqing 400016, Peoples R China
7.Chongqing Univ Canc Hosp, Chongqing Key Lab Translat Res Canc Metastasis &, Chongqing 400030, Peoples R China

Huang, Jiefeng,Li, Jie,Tang, Jun,et al. ZDHHC22-mediated mTOR palmitoylation restrains breast cancer growth and endocrine therapy resistance[J]. International Journal of Biological Sciences,2022,18(7).

Huang, Jiefeng.,Li, Jie.,Tang, Jun.,Wu, Yushen.,Dai, Fengsheng.,...&Xiang, Tingxiu.(2022).ZDHHC22-mediated mTOR palmitoylation restrains breast cancer growth and endocrine therapy resistance.International Journal of Biological Sciences,18(7).

Huang, Jiefeng,et al."ZDHHC22-mediated mTOR palmitoylation restrains breast cancer growth and endocrine therapy resistance".International Journal of Biological Sciences 18.7(2022).