研究动态
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用于研究癌症中的 YAP/TAZ 的工程生物材料和模型系统。

Engineered Biomaterials and Model Systems to Study YAP/TAZ in Cancer.

发表日期:2024 Aug 27
作者: Emma Villares, Sharon Gerecht
来源: Cellular & Molecular Immunology

摘要:

转录共激活因子 yes 相关蛋白 (YAP) 和具有 PDZ 结合基序的转录共激活因子 (TAZ) 是参与多种癌症类型和广泛致瘤事件的主要调节因子,包括癌症干细胞更新、侵袭、转移、肿瘤前体出现和耐药性。已知 YAP/TAZ 受到多种外部线索和刺激的调节,例如细胞外基质硬度、细胞铺展、细胞几何形状和剪切应力。因此,癌症研究领域需要开发和设计相关的体外模型,以准确反映YAP/TAZ信号通路核心的肿瘤微环境的复杂生化和生物物理线索。尽管已经取得了很大进展,但这仍然是推进该领域研究的主要障碍。在这篇综述中,我们重点介绍了当前的工程生物材料和体外模型系统,它们可用于加深我们对 YAP/TAZ 如何塑造癌症多个方面的理解。我们首先讨论当前的 2D 和 3D 水凝胶系统,这些系统模拟 YAP/TAZ 对 ECM 刚度的响应。然后,我们研究了类器官培养系统的当前趋势,以及使用微流体来模拟细胞密度和剪切应力对 YAP/TAZ 的影响。最后,我们分析了当前使用的模型的持续缺陷以及工程系统中未来的重要方向,这将增进我们目前对癌症中 YAP/TAZ 的了解。
The transcriptional coactivators yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) are master regulators involved in a multitude of cancer types and a wide range of tumorigenic events, including cancer stem cell renewal, invasion, metastasis, tumor precursor emergence, and drug resistance. YAP/TAZ are known to be regulated by several external cues and stimuli, such as extracellular matrix stiffness, cell spreading, cell geometry, and shear stress. Therefore, there is a need in the field of cancer research to develop and design relevant in vitro models that can accurately reflect the complex biochemical and biophysical cues of the tumor microenvironment central to the YAP/TAZ signaling nexus. While much progress has been made, this remains a major roadblock to advancing research in this field. In this review, we highlight the current engineered biomaterials and in vitro model systems that can be used to advance our understanding of how YAP/TAZ shapes several aspects of cancer. We begin by discussing current 2D and 3D hydrogel systems that model the YAP/TAZ response to ECM stiffness. We then examine the current trends in organoid culture systems and the use of microfluidics to model the effects of cellular density and shear stress on YAP/TAZ. Finally, we analyze the ongoing pitfalls of the present models used and important future directions in engineering systems that will advance our current knowledge of YAP/TAZ in cancer.