Hippo LATS Pathway in Cancer and Its Role as a Potential Target for Anti-cancer Drugs
摘要
The Hippo pathway is a crucial signalling cascade that controls cell growth, apoptosis, and tissue homeostasis. It was first discovered in Drosophila and is found in many species, including mammals. The pathway involves kinases MST1/2 and LATS1/2, which regulate the transcriptional co-activators Yes-associated protein (YAP) and TAZ. When activated, these kinases prevent YAP and TAZ from entering the nucleus and stimulating gene expression for cell growth and survival. Dysregulation of the Hippo pathway is associated with various cancers, where mutations or abnormal expression of pathway components leads to uncontrolled cell proliferation, evasion of apoptosis, and increased metastasis. This pathway is known to promote migration, invasion and malignancy of cancers. Deregulation of YAP/TAZ signalling is commonly seen in liver, breast, and colon cancers and therefore, targeting the Hippo pathway by blocking YAP/TAZ activation can provide therapeutic opportunities. Enhancing upstream kinases MST1/2 and LATS1/2 could be a promising therapeutic approach. Research is currently exploring small molecules that can disrupt YAP/TAZ-transcriptional enhanced associated domain (TEAD) interactions or promote their cytoplasmic sequestration. Understanding the regulatory mechanisms of the Hippo pathway and its role in cancer may lead to innovative treatments that could improve outcomes for cancer patients.