Hyaluronan Degradation Promotes Cancer via Hippo-YAP Signaling: An Intervention Point for Cancer Therapy.
Takuya OokiMasanori HatakeyamaPublished in: BioEssays : news and reviews in molecular, cellular and developmental biology (2020)
High-molecular-weight hyaluronan acts as a ligand of the tumor-suppressive Hippo signal, whereas degradation of hyaluronan from a high-molecular-weight form to a low-molecular-weight forms by hyaluronidase 2 inhibits Hippo signal activation and thereby activates the pro-oncogenic transcriptional coactivator yes-associated protein (YAP), which creates a cancer-predisposing microenvironment and drives neoplastic transformation of cells through both cell-autonomous and non-cell-autonomous mechanisms. In fact, accumulation of low-molecular-weight hyaluronan in tissue stroma is observed in many types of cancers. Since inhibition of YAP activity suppresses tumor growth in vivo, pharmacological intervention of the Hippo-YAP signal is an attractive approach for future drug development. In this review, pharmacological intervention of excessive hyaluronan degradation as a novel approach for inhibition of the Hippo-YAP signal is also discussed. Development of hyaluronidase inhibitors may provide novel therapeutic strategies for human malignant tumors.
Keyphrases
- randomized controlled trial
- papillary thyroid
- cancer therapy
- single cell
- squamous cell
- cell therapy
- endothelial cells
- transcription factor
- induced apoptosis
- stem cells
- drug delivery
- hyaluronic acid
- gene expression
- childhood cancer
- mesenchymal stem cells
- recombinant human
- physical activity
- young adults
- heat shock protein
- heat shock
- weight loss