The FBXW7-binding sites on FAM83D are potential targets for cancer therapy

IF 6.1 1区 医学 Q1 ONCOLOGY Breast Cancer Research Pub Date : 2024-03-07 DOI:10.1186/s13058-024-01795-9
Xiaoyu Jiang, Yuli Wang, Lulu Guo, Yige Wang, Tianshu Miao, Lijuan Ma, Qin Wei, Xiaoyan Lin, Jian-Hua Mao, Pengju Zhang
{"title":"The FBXW7-binding sites on FAM83D are potential targets for cancer therapy","authors":"Xiaoyu Jiang, Yuli Wang, Lulu Guo, Yige Wang, Tianshu Miao, Lijuan Ma, Qin Wei, Xiaoyan Lin, Jian-Hua Mao, Pengju Zhang","doi":"10.1186/s13058-024-01795-9","DOIUrl":null,"url":null,"abstract":"Increasing evidence shows the oncogenic function of FAM83D in human cancer, but how FAM83D exerts its oncogenic function remains largely unclear. Here, we investigated the importance of FAM83D/FBXW7 interaction in breast cancer (BC). We systematically mapped the FBXW7-binding sites on FAM83D through a comprehensive mutational analysis together with co-immunoprecipitation assay. Mutations at the FBXW7-binding sites on FAM83D led to that FAM83D lost its capability to promote the ubiquitination and proteasomal degradation of FBXW7; cell proliferation, migration, and invasion in vitro; and tumor growth and metastasis in vivo, indicating that the FBXW7-binding sites on FAM83D are essential for its oncogenic functions. A meta-evaluation of FAM83D revealed that the prognostic impact of FAM83D was independent on molecular subtypes. The higher expression of FAM83D has poorer prognosis. Moreover, high expression of FAM83D confers resistance to chemotherapy in BCs, which is experimentally validated in vitro. We conclude that identification of FBXW7-binding sites on FAM83D not only reveals the importance for FAM83D oncogenic function, but also provides valuable insights for drug target.","PeriodicalId":9222,"journal":{"name":"Breast Cancer Research","volume":"68 1","pages":""},"PeriodicalIF":6.1000,"publicationDate":"2024-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Breast Cancer Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s13058-024-01795-9","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Increasing evidence shows the oncogenic function of FAM83D in human cancer, but how FAM83D exerts its oncogenic function remains largely unclear. Here, we investigated the importance of FAM83D/FBXW7 interaction in breast cancer (BC). We systematically mapped the FBXW7-binding sites on FAM83D through a comprehensive mutational analysis together with co-immunoprecipitation assay. Mutations at the FBXW7-binding sites on FAM83D led to that FAM83D lost its capability to promote the ubiquitination and proteasomal degradation of FBXW7; cell proliferation, migration, and invasion in vitro; and tumor growth and metastasis in vivo, indicating that the FBXW7-binding sites on FAM83D are essential for its oncogenic functions. A meta-evaluation of FAM83D revealed that the prognostic impact of FAM83D was independent on molecular subtypes. The higher expression of FAM83D has poorer prognosis. Moreover, high expression of FAM83D confers resistance to chemotherapy in BCs, which is experimentally validated in vitro. We conclude that identification of FBXW7-binding sites on FAM83D not only reveals the importance for FAM83D oncogenic function, but also provides valuable insights for drug target.
查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
FAM83D 上的 FBXW7 结合位点是癌症治疗的潜在靶点
越来越多的证据表明,FAM83D在人类癌症中具有致癌功能,但FAM83D如何发挥其致癌功能在很大程度上仍不清楚。在此,我们研究了FAM83D/FBXW7相互作用在乳腺癌(BC)中的重要性。我们通过全面的突变分析和共沉淀实验系统地绘制了FAM83D上的FBXW7结合位点。FAM83D上的FBXW7结合位点突变导致FAM83D失去了促进FBXW7泛素化和蛋白酶体降解的能力;失去了体外促进细胞增殖、迁移和侵袭的能力;失去了体内促进肿瘤生长和转移的能力,这表明FAM83D上的FBXW7结合位点对其致癌功能至关重要。对 FAM83D 的荟萃评估显示,FAM83D 对预后的影响与分子亚型无关。FAM83D表达越高,预后越差。此外,FAM83D的高表达会使BC对化疗产生耐药性,这在体外实验中得到了验证。我们的结论是,FAM83D上FBXW7结合位点的鉴定不仅揭示了FAM83D致癌功能的重要性,还为药物靶向提供了有价值的见解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 去求助
来源期刊
Breast Cancer Research
Breast Cancer Research 医学-肿瘤学
自引率
0.00%
发文量
76
期刊介绍: Breast Cancer Research is an international, peer-reviewed online journal, publishing original research, reviews, editorials and reports. Open access research articles of exceptional interest are published in all areas of biology and medicine relevant to breast cancer, including normal mammary gland biology, with special emphasis on the genetic, biochemical, and cellular basis of breast cancer. In addition to basic research, the journal publishes preclinical, translational and clinical studies with a biological basis, including Phase I and Phase II trials.
期刊最新文献
Impact of an online decision support tool for ductal carcinoma in situ (DCIS) using a pre-post design (AFT-25) Safety and efficacy of topical testosterone in breast cancer patients receiving ovarian suppression and aromatase inhibitor therapy A triple hormone receptor ER, AR, and VDR signature is a robust prognosis predictor in breast cancer Characteristics and transcriptional regulators of spontaneous epithelial–mesenchymal transition in genetically unperturbed patient-derived non-spindled breast carcinoma CAR expression in invasive breast carcinoma and its effect on adenovirus transduction efficiency
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1