The Crosstalk Between YAP/TAZ and Cancer Metabolism: From Mechanistic Insights to Drug Discovery

As the core transcriptional co-activators of the Hippo signaling pathway, YAP and TAZ play essential roles in maintaining tissue homeostasis and in tumorigenesis. Their aberrant activation is frequently observed in human malignancies, and accumulating evidence has identified them as crucial drivers of tumor initiation and progression. YAP/TAZ have been recently recognized as key regulators of cellular metabolic reprogramming, a hallmark of cancer that fuels tumor cell proliferation by rewiring glucose, lipid, amino acid, and nucleotide metabolism. Conversely, the activity of YAP/TAZ is modulated by metabolites such as glucose and lipids, establishing a complex bidirectional regulatory circuit. Therefore, deciphering this intricate crosstalk is of great importance for cancer therapy and drug discovery. In this review, we systematically clarify the interplay between YAP/TAZ and metabolic reprogramming in cancer, delineate the core molecular networks through which YAP/TAZ govern each metabolic pathway, and summarize the current pharmacological inhibitors targeting YAP/TAZ-regulated metabolic networks. Collectively, these findings pave the way for therapeutic approaches targeting YAP/TAZ-driven metabolic vulnerabilities in cancer.