Prognostic role of TEAD4 in TNBC: in-silico inhibition of the TEAD4-YAP interaction by flufenamic acid analogs.

In silico pharmacology Pub Date : 2024-07-17 eCollection Date: 2024-01-01 DOI:10.1007/s40203-024-00239-8
Shradheya R R Gupta, Shivani Singh, Vanshika Rustagi, Monika Pahuja, Irengbam Rocky Mangangcha, Moses Rinchui, Saurabh K Jha, Archana Singh, Indrakant K Singh
{"title":"Prognostic role of TEAD4 in TNBC: in-silico inhibition of the TEAD4-YAP interaction by flufenamic acid analogs.","authors":"Shradheya R R Gupta, Shivani Singh, Vanshika Rustagi, Monika Pahuja, Irengbam Rocky Mangangcha, Moses Rinchui, Saurabh K Jha, Archana Singh, Indrakant K Singh","doi":"10.1007/s40203-024-00239-8","DOIUrl":null,"url":null,"abstract":"<p><p>Triple-negative breast cancer (TNBC) poses a significant global health challenge due to its highly aggressive nature and invasive characteristics. Dysregulation of the Hippo pathway, a key regulator of various biological processes, is observed in TNBC, and its inhibition holds promise for impeding cancer growth. This in-silico analysis investigates the role of Transcriptional Enhanced Associate Domain 4 (TEAD4) in TNBC and its interaction with Yes Associated Protein (YAP) in cancer progression. Our results demonstrate that TEAD4 upregulation is linked to poor prognosis in TNBC, emphasizing its critical role in the disease. Moreover, we identify CID44521006, an analog of Flufenamic acid, as a potential therapeutic compound capable of disrupting the TEAD4-YAP interaction by binding to the YAP-binding domain of TEAD4. These findings underscore the significance of TEAD4 in TNBC and propose CID44521006 as a promising candidate for therapeutic intervention. The study contributes valuable insights to advance treatment options for TNBC, offering a potential avenue for the development of targeted therapies against this aggressive form of breast cancer.</p><p><strong>Graphical abstract: </strong></p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-024-00239-8.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"12 2","pages":"64"},"PeriodicalIF":0.0000,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11255177/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"In silico pharmacology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1007/s40203-024-00239-8","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/1 0:00:00","PubModel":"eCollection","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0

Abstract

Triple-negative breast cancer (TNBC) poses a significant global health challenge due to its highly aggressive nature and invasive characteristics. Dysregulation of the Hippo pathway, a key regulator of various biological processes, is observed in TNBC, and its inhibition holds promise for impeding cancer growth. This in-silico analysis investigates the role of Transcriptional Enhanced Associate Domain 4 (TEAD4) in TNBC and its interaction with Yes Associated Protein (YAP) in cancer progression. Our results demonstrate that TEAD4 upregulation is linked to poor prognosis in TNBC, emphasizing its critical role in the disease. Moreover, we identify CID44521006, an analog of Flufenamic acid, as a potential therapeutic compound capable of disrupting the TEAD4-YAP interaction by binding to the YAP-binding domain of TEAD4. These findings underscore the significance of TEAD4 in TNBC and propose CID44521006 as a promising candidate for therapeutic intervention. The study contributes valuable insights to advance treatment options for TNBC, offering a potential avenue for the development of targeted therapies against this aggressive form of breast cancer.

Graphical abstract:

Supplementary information: The online version contains supplementary material available at 10.1007/s40203-024-00239-8.

TEAD4在TNBC中的预后作用:氟苯胺酸类似物对TEAD4-YAP相互作用的体内抑制。
三阴性乳腺癌(TNBC)具有高度侵袭性和浸润性的特点,对全球健康构成了重大挑战。Hippo通路是各种生物过程的关键调节因子,在TNBC中观察到Hippo通路失调,抑制Hippo通路有望阻碍癌症生长。本研究对转录增强关联域 4(TEAD4)在 TNBC 中的作用及其与是相关蛋白(YAP)在癌症进展中的相互作用进行了研究。我们的结果表明,TEAD4 的上调与 TNBC 的不良预后有关,强调了它在该疾病中的关键作用。此外,我们还发现氟灭酸的类似物 CID44521006 是一种潜在的治疗化合物,它能与 TEAD4 的 YAP 结合域结合,从而破坏 TEAD4 与 YAP 的相互作用。这些发现强调了TEAD4在TNBC中的重要性,并建议将CID44521006作为治疗干预的候选药物。这项研究为推动 TNBC 的治疗方案提供了宝贵的见解,为开发针对这种侵袭性乳腺癌的靶向疗法提供了潜在的途径:在线版本包含补充材料,可在 10.1007/s40203-024-00239-8上查阅。
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 求助全文
来源期刊
自引率
0.00%
发文量
0
×
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
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
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 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信