Abstract
Osteosarcoma and Ewing sarcoma are the most prevalent bone pediatric tumors. Despite intensive basic and medical research studies to discover new therapeutics and to improve current treatments, almost 40% of osteosarcoma and Ewing sarcoma patients succumb to the disease. Patients with poor prognosis are related to either the presence of metastases at diagnosis or resistance to chemotherapy. Over the past ten years, considerable interest for the Hippo/YAP signaling pathway has taken place within the cancer research community. This signaling pathway operates at different steps of tumor progression: Primary tumor growth, angiogenesis, epithelial to mesenchymal transition, and metastatic dissemination. This review discusses the current knowledge about the involvement of the Hippo signaling pathway in cancer and specifically in paediatric bone sarcoma progression.
Highlights
First Discoveries about the Hippo Signaling PathwayThe Hippo signaling pathway was discovered at the end of the 20st century, when it was first described as a key regulator of tissue growth in Drosophila
When the Hippo signaling pathway is inactive, YAP is not phosphorylated and translocates to the nucleus where it can exert its transcriptional activity by binding to TEAD
A more recent study conducted on a larger number of patients demonstrated that a high expression of YAP is associated with a poor prognosis, which suggests that the Hippo signaling pathway plays a key role in Ewing’s sarcoma (EWs) progression
Summary
The Hippo signaling pathway was discovered at the end of the 20st century, when it was first described as a key regulator of tissue growth in Drosophila. In 1995, Noll and Bryant [1] in addition to Stewart and Yu [2] demonstrated aberrant and strong tissue growth in Drosophila in response to a loss of Wst (warts) protein expression This was the start of many studies on the partner factors of the Hippo signaling pathway. A functional and biochemical characterization of the Salvador-Warts-Hippo signaling pathway was established [6,7]. This corresponds to a cascade of phosphorylation by protein kinases, in which Hpo phosphorylates and activates Wts, which in turn represses the transcription of target genes via a transcription inhibitor unknown at that time. Recent studies have further implicated the Hippo pathway in various physiological processes and other pathologies, such as the regulation of stem cell differentiation, tissue regeneration, immunity, or cancer
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