• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

ZDHHC22 介导的 mTOR 棕榈酰化抑制乳腺癌生长和内分泌治疗耐药性。

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

机构信息

Department of Breast and Thyroid Surgery, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen 518020, Guangdong, China.

Department of General Surgery, Shenzhen People's Hospital, Shenzhen 518020, Guangdong, China.

出版信息

Int J Biol Sci. 2022 Apr 4;18(7):2833-2850. doi: 10.7150/ijbs.70544. eCollection 2022.

DOI:10.7150/ijbs.70544
PMID:35541896
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9066102/
Abstract

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.

摘要

棕榈酰化对于调控蛋白质稳定性和蛋白质-蛋白质相互作用的经典癌症特征至关重要。ZDHHC22 作为棕榈酰转移酶家族的知名成员，其在癌症中的作用尚未被揭示。我们发现 ZDHHC22 在雌激素受体（ER）阴性乳腺癌（BrCa）组织和细胞系中的表达显著降低，并且其表达与 BrCa 患者的临床预后呈正相关。ZDHHC22 的低表达可能是由于其启动子甲基化所致。ZDHHC22 抑制了 BrCa 细胞在体外和体内的增殖能力，这取决于其编码的棕榈酰转移酶活性。在机制方面，ZDHHC22 通过棕榈酰化降低了 mTOR 的稳定性，并降低了 AKT 信号通路的激活。此外，ZDHHC22 的异位表达可以恢复 MCF-7R 细胞对他莫昔芬治疗的敏感性。总之，ZDHHC22 可能作为一种预后生物标志物和治疗靶点，为探索针对特定棕榈酰化药物提供理论基础，特别是对于内分泌治疗耐药的 BrCa 患者。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5cf/9066102/39268c9a7336/ijbsv18p2833g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5cf/9066102/de7c017e7740/ijbsv18p2833g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5cf/9066102/31f786689ad7/ijbsv18p2833g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5cf/9066102/be7fcb49d278/ijbsv18p2833g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5cf/9066102/0bae51626910/ijbsv18p2833g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5cf/9066102/980e8d0dfc0a/ijbsv18p2833g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5cf/9066102/c510724b37fe/ijbsv18p2833g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5cf/9066102/611d77fb86d1/ijbsv18p2833g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5cf/9066102/e5fdef638620/ijbsv18p2833g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5cf/9066102/39268c9a7336/ijbsv18p2833g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5cf/9066102/de7c017e7740/ijbsv18p2833g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5cf/9066102/31f786689ad7/ijbsv18p2833g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5cf/9066102/be7fcb49d278/ijbsv18p2833g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5cf/9066102/0bae51626910/ijbsv18p2833g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5cf/9066102/980e8d0dfc0a/ijbsv18p2833g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5cf/9066102/c510724b37fe/ijbsv18p2833g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5cf/9066102/611d77fb86d1/ijbsv18p2833g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5cf/9066102/e5fdef638620/ijbsv18p2833g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5cf/9066102/39268c9a7336/ijbsv18p2833g009.jpg

相似文献

1
ZDHHC22-mediated mTOR palmitoylation restrains breast cancer growth and endocrine therapy resistance.ZDHHC22 介导的 mTOR 棕榈酰化抑制乳腺癌生长和内分泌治疗耐药性。
Int J Biol Sci. 2022 Apr 4;18(7):2833-2850. doi: 10.7150/ijbs.70544. eCollection 2022.
2
MICAL-L2, as an estrogen-responsive gene, is involved in ER-positive breast cancer cell progression and tamoxifen sensitivity via the AKT/mTOR pathway.MICAL-L2 作为一个雌激素反应基因，通过 AKT/mTOR 通路参与 ER 阳性乳腺癌细胞的进展和他莫昔芬敏感性。
Biochem Pharmacol. 2024 Jul;225:116256. doi: 10.1016/j.bcp.2024.116256. Epub 2024 May 9.
3
Acquisition of epithelial-mesenchymal transition phenotype in the tamoxifen-resistant breast cancer cell: a new role for G protein-coupled estrogen receptor in mediating tamoxifen resistance through cancer-associated fibroblast-derived fibronectin and β1-integrin signaling pathway in tumor cells.他莫昔芬耐药乳腺癌细胞中上皮-间质转化表型的获得：G蛋白偶联雌激素受体在通过肿瘤相关成纤维细胞衍生的纤连蛋白和肿瘤细胞中的β1整合素信号通路介导他莫昔芬耐药中的新作用。
Breast Cancer Res. 2015 May 21;17(1):69. doi: 10.1186/s13058-015-0579-y.
4
Impact of dual mTORC1/2 mTOR kinase inhibitor AZD8055 on acquired endocrine resistance in breast cancer in vitro.双mTORC1/2 mTOR激酶抑制剂AZD8055对体外乳腺癌获得性内分泌耐药的影响
Breast Cancer Res. 2014 Jan 23;16(1):R12. doi: 10.1186/bcr3604.
5
Overcoming endocrine resistance due to reduced PTEN levels in estrogen receptor-positive breast cancer by co-targeting mammalian target of rapamycin, protein kinase B, or mitogen-activated protein kinase kinase.通过共同靶向雷帕霉素哺乳动物靶蛋白、蛋白激酶B或丝裂原活化蛋白激酶激酶克服雌激素受体阳性乳腺癌中因PTEN水平降低导致的内分泌抵抗。
Breast Cancer Res. 2014 Sep 11;16(5):430. doi: 10.1186/s13058-014-0430-x.
6
Luminal breast cancer cell lines overexpressing ZNF703 are resistant to tamoxifen through activation of Akt/mTOR signaling.过表达 ZNF703 的腔面乳腺癌细胞系通过激活 Akt/mTOR 信号对他莫昔芬产生耐药性。
PLoS One. 2013 Aug 26;8(8):e72053. doi: 10.1371/journal.pone.0072053. eCollection 2013.
7
Effects of Combined Pentadecanoic Acid and Tamoxifen Treatment on Tamoxifen Resistance in MCF-7/SC Breast Cancer Cells.联合十五烷酸和他莫昔芬治疗对 MCF-7/SC 乳腺癌细胞他莫昔芬耐药的影响。
Int J Mol Sci. 2022 Sep 26;23(19):11340. doi: 10.3390/ijms231911340.
8
AKT Antagonist AZD5363 Influences Estrogen Receptor Function in Endocrine-Resistant Breast Cancer and Synergizes with Fulvestrant (ICI182780) In Vivo.AKT拮抗剂AZD5363影响内分泌抵抗性乳腺癌中的雌激素受体功能并在体内与氟维司群（ICI182780）协同作用。
Mol Cancer Ther. 2015 Sep;14(9):2035-48. doi: 10.1158/1535-7163.MCT-15-0143. Epub 2015 Jun 26.
9
Inhibitory role of large intergenic noncoding RNA-ROR on tamoxifen resistance in the endocrine therapy of breast cancer by regulating the PI3K/Akt/mTOR signaling pathway.长链非编码 RNA-ROR 通过调控 PI3K/Akt/mTOR 信号通路抑制乳腺癌内分泌治疗中他莫昔芬耐药的作用。
J Cell Physiol. 2019 Feb;234(2):1904-1912. doi: 10.1002/jcp.27066. Epub 2018 Aug 26.
10
Tumor-associated macrophages secrete CC-chemokine ligand 2 and induce tamoxifen resistance by activating PI3K/Akt/mTOR in breast cancer.肿瘤相关巨噬细胞通过激活乳腺癌中的 PI3K/Akt/mTOR 分泌 CC 趋化因子配体 2 并诱导他莫昔芬耐药。
Cancer Sci. 2020 Jan;111(1):47-58. doi: 10.1111/cas.14230. Epub 2019 Dec 19.

引用本文的文献

1
Recent advances in S-palmitoylation and its emerging roles in human diseases.S-棕榈酰化的最新进展及其在人类疾病中的新作用。
J Hematol Oncol. 2025 Sep 1;18(1):83. doi: 10.1186/s13045-025-01738-7.
2
Palmitoylation: an emerging therapeutic target bridging physiology and disease.棕榈酰化：连接生理与疾病的新兴治疗靶点。
Cell Mol Biol Lett. 2025 Aug 15;30(1):98. doi: 10.1186/s11658-025-00776-w.
3
Palmitic acid and palmitoylation in cancer: Understanding, insights, and challenges.癌症中的棕榈酸与棕榈酰化：认识、见解与挑战

本文引用的文献

1
Lipid-induced S-palmitoylation as a Vital Regulator of Cell Signaling and Disease Development.脂质诱导的S-棕榈酰化作为细胞信号传导和疾病发展的重要调节因子。
Int J Biol Sci. 2021 Oct 11;17(15):4223-4237. doi: 10.7150/ijbs.64046. eCollection 2021.
2
Cancer cells escape p53's tumor suppression through ablation of ZDHHC1-mediated p53 palmitoylation.癌细胞通过消除 ZDHHC1 介导的 p53 棕榈酰化来逃避 p53 的肿瘤抑制作用。
Oncogene. 2021 Sep;40(35):5416-5426. doi: 10.1038/s41388-021-01949-5. Epub 2021 Jul 19.
3
NS1-mediated upregulation of ZDHHC22 acyltransferase in influenza a virus infected cells.
Innovation (Camb). 2025 Apr 29;6(8):100918. doi: 10.1016/j.xinn.2025.100918. eCollection 2025 Aug 4.
4
Multi-omics insights into Palmitoylation-mediated brain network remodeling and glioblastoma risk.对棕榈酰化介导的脑网络重塑和胶质母细胞瘤风险的多组学见解。
Discov Oncol. 2025 Aug 8;16(1):1507. doi: 10.1007/s12672-025-03369-3.
5
Role of S-palmitoylation in digestive system diseases.S-棕榈酰化在消化系统疾病中的作用。
Cell Death Discov. 2025 Jul 18;11(1):331. doi: 10.1038/s41420-025-02629-z.
6
S-palmitoylation: a novel insight in the development and immunotherapy of oral squamous cell carcinoma.S-棕榈酰化：口腔鳞状细胞癌发生发展及免疫治疗的新见解
J Cancer. 2025 Jun 12;16(9):2787-2799. doi: 10.7150/jca.110721. eCollection 2025.
7
C1QL1 inhibits breast cancer through the HSP90α/VCP-ERS/UPR axis.C1QL1通过HSP90α/VCP-ERS/UPR轴抑制乳腺癌。
Exp Mol Med. 2025 Jun;57(6):1308-1323. doi: 10.1038/s12276-025-01486-1. Epub 2025 Jun 30.
8
Recent Overview of Protein Palmitoylation and Profiling Methodologies.蛋白质棕榈酰化及其分析方法的最新综述
Methods Mol Biol. 2025;2921:361-370. doi: 10.1007/978-1-0716-4502-4_20.
9
Protein lipidation in the tumor microenvironment: enzymology, signaling pathways, and therapeutics.肿瘤微环境中的蛋白质脂化：酶学、信号通路与治疗学
Mol Cancer. 2025 May 7;24(1):138. doi: 10.1186/s12943-025-02309-7.
10
Palmitoylation in cardiovascular diseases: Molecular mechanism and therapeutic potential.心血管疾病中的棕榈酰化：分子机制与治疗潜力
Int J Cardiol Heart Vasc. 2025 Apr 4;58:101675. doi: 10.1016/j.ijcha.2025.101675. eCollection 2025 Jun.
流感 A 病毒感染细胞中 NS1 介导的 ZDHHC22 酰基转移酶的上调。
Cell Microbiol. 2021 Jun;23(6):e13322. doi: 10.1111/cmi.13322. Epub 2021 Mar 9.
4
PI3K/AKT/mTOR Signaling Pathway in Breast Cancer: From Molecular Landscape to Clinical Aspects.PI3K/AKT/mTOR 信号通路在乳腺癌中的作用：从分子特征到临床应用。
Int J Mol Sci. 2020 Dec 26;22(1):173. doi: 10.3390/ijms22010173.
5
The emerging roles of ZDHHCs-mediated protein palmitoylation in the antiviral innate immune responses.ZDHHCs 介导的蛋白质棕榈酰化在抗病毒天然免疫反应中的新作用。
Crit Rev Microbiol. 2021 Feb;47(1):34-43. doi: 10.1080/1040841X.2020.1835821. Epub 2020 Oct 26.
6
DNA methylation downregulated ZDHHC1 suppresses tumor growth by altering cellular metabolism and inducing oxidative/ER stress-mediated apoptosis and pyroptosis.DNA 甲基化下调 ZDHHC1 通过改变细胞代谢并诱导氧化/内质网应激介导的细胞凋亡和细胞焦亡来抑制肿瘤生长。
Theranostics. 2020 Jul 25;10(21):9495-9511. doi: 10.7150/thno.45631. eCollection 2020.
7
Enhancer-Driven lncRNA BDNF-AS Induces Endocrine Resistance and Malignant Progression of Breast Cancer through the RNH1/TRIM21/mTOR Cascade.增强子驱动的长链非编码 RNA BDNF-AS 通过 RNH1/TRIM21/mTOR 级联诱导乳腺癌内分泌耐药和恶性进展。
Cell Rep. 2020 Jun 9;31(10):107753. doi: 10.1016/j.celrep.2020.107753.
8
Hyperactivation of TORC1 Drives Resistance to the Pan-HER Tyrosine Kinase Inhibitor Neratinib in HER2-Mutant Cancers.TORC1的过度激活导致HER2突变型癌症对泛HER酪氨酸激酶抑制剂奈拉替尼产生耐药性。
Cancer Cell. 2020 Feb 10;37(2):258-259. doi: 10.1016/j.ccell.2020.01.010.
9
Tumor suppressive BTB/POZ zinc-finger protein ZBTB28 inhibits oncogenic BCL6/ZBTB27 signaling to maintain p53 transcription in multiple carcinogenesis.抑瘤性 BTB/POZ 锌指蛋白 ZBTB28 抑制致癌性 BCL6/ZBTB27 信号通路以维持多种癌症发生过程中的 p53 转录。
Theranostics. 2019 Oct 18;9(26):8182-8195. doi: 10.7150/thno.34983. eCollection 2019.
10
mTOR: Role in cancer, metastasis and drug resistance.mTOR：在癌症、转移和耐药性中的作用。
Semin Cancer Biol. 2019 Dec;59:92-111. doi: 10.1016/j.semcancer.2019.07.003. Epub 2019 Aug 10.