YAP1 Is a Crucial Nexus in the Tumor Microenvironment.

Area of Science:

• Oncology
• Molecular Biology
• Cancer Signaling

Background:

• Yes-associated protein-1 (YAP1) is a key effector of the Hippo signaling pathway, implicated in various cancers.
• YAP1 promotes critical cancer hallmarks like uncontrolled growth, drug resistance, and metastasis.
• Solid tumors involve complex interactions between malignant and nonmalignant cells within the tumor microenvironment (TME).

Purpose of the Study:

• To review the multifaceted roles of YAP1 within different tumor microenvironment compartments.
• To elucidate how YAP1 signaling in nonmalignant cells contributes to cancer progression.
• To summarize YAP1 inhibitor development and their therapeutic potential.

Main Methods:

• Comprehensive literature review of YAP1's function in cancer and the TME.
• Analysis of YAP1's downstream signaling in various cell types within the TME.
• Summary of current YAP1 inhibitors and their clinical implications.

Main Results:

• YAP1 significantly influences cancer-associated fibroblasts (CAFs), immune cells, endothelial cells, and exosomes.
• Reciprocal interactions mediated by YAP1 between malignant and nonmalignant cells fuel tumor growth and metastasis.
• YAP1 targeting demonstrates promise, particularly in combination therapies.

Conclusions:

• YAP1's role extends beyond cancer cells to critically impact the TME, driving cancer progression.
• Targeting YAP1 in the TME presents a promising therapeutic avenue for difficult-to-treat cancers.
• Further research into YAP1 inhibitors and combination strategies is warranted.