Journal
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
Volume 18, Issue 7, Pages 2833-2850Publisher
IVYSPRING INT PUBL
DOI: 10.7150/ijbs.70544
Keywords
Breast cancer; ZDHHC22; Palmitoylation; mTOR; Endocrine therapy resistance
Categories
Funding
- National Natural Science Foundation of China [82172619, 31420103915]
- Natural Science Foundation of Chongqing [CSTC2021jscx-gksb-N0023, 2019ZX002]
- Shenzhen Key Medical Discipline Construction Fund [SZXK015]
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This article reveals the important role of ZDHHC22 in breast cancer and its correlation with patient prognosis. ZDHHC22 inhibits the proliferation of breast cancer cells by regulating protein stability and signaling pathway activation. It has the potential to serve as a therapeutic target for endocrine therapy-resistant breast cancer patients.
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.
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