Cells within tissues are subject to various mechanical forces, including hydrostatic pressure, shear stress, compression, and tension. These mechanical stimuli can be converted into biochemical signals through mechanoreceptors or cytoskeleton-dependent response processes, shaping the microenvironment and maintaining cellular physiological balance. Several studies have demonstrated the roles of Yes-associated protein (YAP) and its homolog transcriptional coactivator with PDZ-binding motif (TAZ) as mechanotransducers, exerting dynamic influence on cellular phenotypes including differentiation and disease pathogenesis. This regulatory function entails the involvement of the cytoskeleton, nucleoskeleton, integrin, focal adhesions (FAs), and the integration of multiple signaling pathways, including extracellular signal-regulated kinase (ERK), wingless/integrated (WNT), and Hippo signaling. Furthermore, emerging evidence substantiates the implication of long non-coding RNAs (lncRNAs) as mechanosensitive molecules in cellular mechanotransduction. In this review, we discuss the mechanisms through which YAP/TAZ and lncRNAs serve as effectors in responding to mechanical stimuli. Additionally, we summarize and elaborate on the crucial signal molecules involved in mechanotransduction.
细胞在组织中受到各种机械力的作用，包括静水压力、剪切应力、压缩和张力。这些机械刺激可通过机械感受器或细胞骨架依赖性反应过程转化为生化信号，从而塑造微环境，并维持细胞生理平衡。研究已证实转录共激活因子YAP/TAZ可作为机械转导因子，对细胞表型（如分化和疾病发病）产生动态影响。这种调节功能涉及细胞骨架、核骨架、整合素、局灶黏附蛋白（FA），以及多种信号通路的整合，包括细胞外信号调节蛋白激酶（ERK）、WNT和Hippo信号通路。此外，最新研究表明长链非编码RNA（lncRNA）可作为机械敏感分子在机械转导过程中发挥作用。本综述讨论了YAP/TAZ和lncRNA响应机械刺激的机制，并总结了参与机械转导的关键信号分子。.

UNASSIGNED: The Hippo pathway represents a new opportunity for the treatment of cancer. Overexpression of Yes-associated protein (YAP) or transcriptional coactivator with PDZ-binding motif (TAZ) or TEAD has been demonstrated in cancers and YAP mediates resistance to cancer drugs. Since 2018, the potential of this pathway has been illustrated by numerous articles and patents and the first drugs entering in clinical trial phase 1.
UNASSIGNED: This review is limited to published patent applications that have disclosed direct small-molecule inhibitors of the YAP/TAZ-TEAD interaction.
UNASSIGNED: The YAP/TAZ-TEAD transcriptional complex is a promising target for the treatment of cancer. Approximately 30 international patents (used database: Sci-finder, query: TEAD; documents: patents; period: from 2017-January 2022) that disclose TEAD transcriptional inhibitors have been filled since 2018. The mechanism of action is not always described in the patents, we can divide the drugs into three different categories: (i) external TEAD ligands; (ii) non-covalent TEAD ligands of the palmitate pocket; (iii) covalent TEAD ligands, which bind into the palmitate pocket. The first molecules in clinical trial phase 1 are non-covalent TEAD ligands. The selective TEAD ligand have also been patented, published and selectivity could be of great interest for personalized medicine.

BACKGROUND: The Hippo pathway is widely considered to inhibit cell growth and play an important role in regulating the size of organs. However, recent studies have shown that abnormal regulation of the Hippo pathway can also affect tumor invasion and metastasis. Therefore, finding out how the Hippo pathway promotes tumor development by regulating the expression of target genes provides new ideas for future research on targeted drugs that inhibit tumor progression.
METHODS: PubMed, Embase, Web of Science, and the Cochrane Library were systematically searched.
RESULTS: The search strategy identified 1892 hits and 196 publications were finally included in this review. As the core molecule of the Hippo pathway, YAP/TAZ are usually highly expressed in tumors that undergo invasion and migration and are accompanied by abnormally strong nuclear metastasis. Through its interaction with nuclear transcription factors TEADs, it directly or indirectly regulates and the expressions of target genes related to tumor metastasis and invasion. These target genes can induce the formation of invasive pseudopodia in tumor cells, reduce intercellular adhesion, degrade extracellular matrix (ECM), and cause epithelial-mesenchymal transition (EMT), or indirectly promote through other signaling pathways, such as mitogen-activated protein kinases (MAPK), TGF/Smad, etc, which facilitate the invasion and metastasis of tumors.
CONCLUSIONS: This article mainly introduces the research progress of YAP/TAZ which are the core molecules of the Hippo pathway regulating related target genes to promote tumor invasion and metastasis. Focus on the target genes that affect tumor invasion and metastasis, providing the possibility for the selection of clinical drug treatment targets, to provide some help for a more in-depth study of tumor invasion and migration mechanism and the development of clinical drugs.