Emerging roles of Hippo signaling pathway in gastrointestinal cancers and its molecular mechanisms

Abstract

Hippo signaling pathway is highly conservative in evolution. MST1/2, LATS1/2, and the effector protein YAP/TAZ are the core members of this signaling pathway in mammalian cells. There have been many studies on YAP/TAZ and its downstream, however, the upstream regulatory factors of the Hippo signaling pathway remain unclear, and become one of the hot research directions of this pathway at present. In addition, Hippo signaling pathway can cross-talk with other signaling pathways such as Wnt and Notch signaling pathways, and plays an important role in controlling organ size, maintaining tissue homeostasis, and promoting tissue repair and regeneration. Abnormal Hippo signaling pathway may lead to the occurrence of a variety of tumors, especially gastrointestinal cancers such as liver cancer, colorectal cancer and gastric cancer. The abnormal expression of its members in gastrointestinal cancers is related to cancer cell proliferation, apoptosis, invasion and migration. Hippo signaling pathway is vital for liver repair and regeneration. Its inactivation will lead to the occurrence of primary liver cancer. The mechanism of YAP in liver cancer mainly depends on TEAD-mediated gene transcription. Hippo signaling pathway is also important for maintaining intestinal homeostasis, and its imbalance can lead to the occurrence and recurrence of colorectal cancer. In primary and metastatic gastric cancer, the expression of YAP/TAZ is significantly up-regulated, but the specific molecular mechanism is unclear. This article summarizes the recent progress on Hippo signaling pathway and its upstream regulatory factors, its roles in the development of gastrointestinal cancers and related molecular mechanisms; and also discusses the future research directions of Hippo signaling pathway.