Shradheya R R Gupta, Shivani Singh, Vanshika Rustagi, Monika Pahuja, Irengbam Rocky Mangangcha, Moses Rinchui, Saurabh K Jha, Archana Singh, Indrakant K Singh
{"title":"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。","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":"{\"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}","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}
Prognostic role of TEAD4 in TNBC: in-silico inhibition of the TEAD4-YAP interaction by flufenamic acid analogs.
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.