Hippo signaling in cancer: regulatory mechanisms and therapeutic strategies

Abstract

As an evolutionarily conserved pathway, Hippo signaling not only plays a key role in embryonic development, but also regulates the initiation and progression of cancer. The upstream factors regulating the Hippo pathway are complex, including cell-cell contact, cell-extracellular matrix contact, membrane receptor-ligand binding, and cytoskeletal tension. In response to these mechanical or soluble cues, the Hippo core kinases are activated or inactivated, regulating the activity of key transcription co-factor YAP/TAZ thus yielding biological consequences. In the context of neoplasm, dysregulation of Hippo signaling contributes to cancer hallmarks such as sustained proliferation, stem-like properties, and metastasis. Importantly, targeting Hippo signaling by chemicals is emerging as a promising anticancer strategy. This article briefly introduces the discovery process of the Hippo pathway, summarizes the upstream signals regulating the Hippo pathway, discusses the relationship between Hippo inactivation and cancer development, and highlights the potential use of chemicals targeting Hippo signaling in cancer treatment.