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.
Cite this paper
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