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TEAD4在三阴性乳腺癌中的预后作用:氟芬那酸类似物对TEAD4-YAP相互作用的计算机模拟抑制

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

作者信息

Gupta Shradheya R R, Singh Shivani, Rustagi Vanshika, Pahuja Monika, Mangangcha Irengbam Rocky, Rinchui Moses, Jha Saurabh K, Singh Archana, Singh Indrakant K

机构信息

Molecular Biology Research Laboratory, Department of Zoology, & DBC I4 Centre, Deshbandhu College, University of Delhi, New Delhi, 110019 India.

Department of Biotechnology, Sharda School of Engineering and Technology, Sharda University, Greater Noida, 201310 India.

出版信息

In Silico Pharmacol. 2024 Jul 17;12(2):64. doi: 10.1007/s40203-024-00239-8. eCollection 2024.

Abstract

UNLABELLED

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.

SUPPLEMENTARY INFORMATION

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

摘要

未标记

三阴性乳腺癌(TNBC)因其高度侵袭性和浸润性特征,对全球健康构成重大挑战。在TNBC中观察到 Hippo 通路失调,该通路是各种生物过程的关键调节因子,抑制该通路有望阻碍癌症生长。这项计算机模拟分析研究了转录增强关联结构域 4(TEAD4)在TNBC中的作用及其在癌症进展中与 Yes 相关蛋白(YAP)的相互作用。我们的结果表明,TEAD4上调与TNBC的不良预后相关,强调了其在该疾病中的关键作用。此外,我们鉴定出氟芬那酸类似物CID44521006,它是一种潜在的治疗化合物,能够通过与TEAD4的YAP结合结构域结合来破坏TEAD4-YAP相互作用。这些发现强调了TEAD4在TNBC中的重要性,并提出CID44521006作为治疗干预的有希望的候选药物。该研究为推进TNBC的治疗选择提供了有价值的见解,为开发针对这种侵袭性乳腺癌的靶向治疗提供了一条潜在途径。

补充信息

在线版本包含可在10.1007/s40203-024-00239-8获取的补充材料。

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TEAD4 as an Oncogene and a Mitochondrial Modulator.TEAD4作为一种癌基因和线粒体调节剂。
Front Cell Dev Biol. 2022 May 5;10:890419. doi: 10.3389/fcell.2022.890419. eCollection 2022.
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The two sides of Hippo pathway in cancer. Hippo 通路在癌症中的两面性。
Semin Cancer Biol. 2022 Oct;85:33-42. doi: 10.1016/j.semcancer.2021.07.006. Epub 2021 Jul 13.

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