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
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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.

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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。
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