Potential Role of Hippo-Signaling Pathway in Gastric Cancer

摘要

Gastric cancer is one of the most common malignancies worldwide. Understanding the molecular nature of gastric cancer is essential for the development of effective and personalized therapies. Several molecular signal transduction pathways drive tumorgenesis when deregulated and responded to different types of therapeutic interventions. The Hippo signaling pathway has been demonstrated to play a central role in the development and regulation of tissues and organ size. The deregulation of Hippo signaling leads to a concurrent combination of uncontrolled cellular proliferation and inhibition of apoptosis, two key hall marks in cancer development. The molecular nature of this pathway was first uncovered in Drosophila melanogaster through genetic screens to identify regulators of cell growth and cell division. The pathway is strongly conserved in humans, and rendering Drosophila is a suitable and efficient model system to better understand the molecular nature of this pathway. Current studies have demonstrated that a variety of deregulated molecules can alter Hippo signaling, leading to the constitutive activation of the transcriptional activator YAP or its paralog TAZ. Additionally, the Hippo-signaling pathway integrates inputs from a number of growth signaling pathways, positioning the Hippo-signaling pathway in a central role in the regulation of tissue size. Importantly, deregulated Hippo signaling is frequently observed in human cancers. YAP is commonly activated in a number of in vitro and in vivo models of tumorogenesis, as well as a number of gastric cancers. The common activation of YAP in many different tumor types and in gastric cancer provides an attractive target for potential therapeutic intervention. In this review, we appraise the evidence for the Hippo-signaling pathway as a cancer signaling network, and discuss cancer-relevant biological functions, potential mechanisms by which Hippo-signaling pathway activity is altered in cancer and emerging therapeutic strategies.