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

Area of Science:

• Biomedical Engineering
• Cancer Biology
• Biomaterials Science

Background:

• Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) are key regulators in various cancers and tumorigenic processes.
• YAP/TAZ activity is influenced by biophysical cues like extracellular matrix stiffness, cell shape, and shear stress within the tumor microenvironment.
• Accurate in vitro models are needed to study YAP/TAZ signaling in cancer.

Purpose of the Study:

• To review engineered biomaterials and in vitro systems for studying YAP/TAZ signaling in cancer.
• To highlight models that mimic tumor microenvironment biophysical cues relevant to YAP/TAZ.
• To analyze current model limitations and future directions for YAP/TAZ research.

Main Methods:

• Review of 2D and 3D hydrogel systems assessing YAP/TAZ response to matrix stiffness.
• Examination of organoid culture systems and microfluidics for modeling YAP/TAZ response to cell density and shear stress.
• Analysis of current model pitfalls and future engineering strategies.

Main Results:

• Engineered biomaterials and in vitro models offer insights into YAP/TAZ's role in cancer stem cell renewal, invasion, metastasis, and drug resistance.
• Hydrogels, organoids, and microfluidic systems are being developed to recapitulate tumor microenvironment conditions affecting YAP/TAZ.
• Significant challenges remain in fully replicating the complex tumor milieu for YAP/TAZ studies.

Conclusions:

• Advanced engineered in vitro models are essential for dissecting the multifaceted roles of YAP/TAZ in cancer.
• Future research should focus on refining these models to better predict YAP/TAZ's impact on tumorigenesis and therapeutic response.
• Overcoming current model limitations will accelerate the development of targeted cancer therapies.