Research on the Hippo Pathway in Cancer

The Hippo, as a central pathway regulating cell proliferation, apoptosis, stem cell homeostasis and organ development, is closely associated with the onset and progression of tumors, metabolic reprogramming, drug resistance and immune evasion when it is abnormally inactivated. The Hippo not only directly promotes tumor cell proliferation, maintains cancer stem cell properties, and mediates metabolic reprogramming and treatment resistance, but also reshapes the tumor microenvironment(TME) by regulating the formation, heterogeneity and function of cancer-associated fibroblasts (CAFs). Furthermore, it mediates tumor immunosuppression and immune evasion by modulating programmed death-ligand 1(PD-L1) expression, T-cell function, macrophage polarization and cytokine secretion. At the same time, inflammatory cytokines, growth factors, metabolites and physical signals within the TME can negatively regulate the activity of the Hippo, creating a pro-tumor positive feedback loop. This article provides a systematic review of the composition and regulation of the Hippo , its mechanisms of action in the biological behavior of tumor cells and interactions within the tumor microenvironment, as well as progress in the development of drugs targeting this pathway. It offers a theoretical basis for a deeper understanding of the role of the Hippo in tumors and for the development of novel anti-tumor therapeutic strategies.