The role of the Hippo pathway in human disease and tumorigenesis
Abstract Understanding the molecular nature of human cancer is essential to the development of effective and personalized therapies. Several different molecular signal transduction pathways drive tumorigenesis when deregulated and respond to different types of therapeutic interventions. The Hippo si...
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| Format: | Article |
| Language: | English |
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Wiley
2014-12-01
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| Series: | Clinical and Translational Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/2001-1326-3-25 |
| _version_ | 1828461977005981696 |
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| author | Daniel A Barron Jacob D Kagey |
| author_facet | Daniel A Barron Jacob D Kagey |
| author_sort | Daniel A Barron |
| collection | DOAJ |
| description | Abstract Understanding the molecular nature of human cancer is essential to the development of effective and personalized therapies. Several different molecular signal transduction pathways drive tumorigenesis when deregulated and respond to different types of therapeutic interventions. The Hippo signaling pathway has been demonstrated to play a central role in the regulation of tissue and organ size during development. The deregulation of Hippo signaling leads to a concurrent combination of uncontrolled cellular proliferation and inhibition of apoptosis, two key hallmarks 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, rendering Drosophila a suitable and efficient model system to better understand the molecular nature of this pathway. In the present study, we review the current understanding of the molecular mechanism and clinical impact of the Hippo 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 pathway integrates inputs from a number of growth signaling pathways, positioning the Hippo 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 tumorigenesis, as well as a number of human cancers. The common activation of YAP in many different tumor types provides an attractive target for potential therapeutic intervention. |
| first_indexed | 2024-12-11T02:28:08Z |
| format | Article |
| id | doaj.art-7735dc9a9cd44e4bb343abfd59d143d3 |
| institution | Directory Open Access Journal |
| issn | 2001-1326 |
| language | English |
| last_indexed | 2024-12-11T02:28:08Z |
| publishDate | 2014-12-01 |
| publisher | Wiley |
| record_format | Article |
| series | Clinical and Translational Medicine |
| spelling | doaj.art-7735dc9a9cd44e4bb343abfd59d143d32022-12-22T01:23:53ZengWileyClinical and Translational Medicine2001-13262014-12-0131n/an/a10.1186/2001-1326-3-25The role of the Hippo pathway in human disease and tumorigenesisDaniel A Barron0Jacob D Kagey1Department of Cell BiologyEmory University School of MedicineAtlantaGAUSADepartment of BiologyUniversity of Detroit Mercy4001 West McNichols RoadDetroitMIUSAAbstract Understanding the molecular nature of human cancer is essential to the development of effective and personalized therapies. Several different molecular signal transduction pathways drive tumorigenesis when deregulated and respond to different types of therapeutic interventions. The Hippo signaling pathway has been demonstrated to play a central role in the regulation of tissue and organ size during development. The deregulation of Hippo signaling leads to a concurrent combination of uncontrolled cellular proliferation and inhibition of apoptosis, two key hallmarks 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, rendering Drosophila a suitable and efficient model system to better understand the molecular nature of this pathway. In the present study, we review the current understanding of the molecular mechanism and clinical impact of the Hippo 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 pathway integrates inputs from a number of growth signaling pathways, positioning the Hippo 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 tumorigenesis, as well as a number of human cancers. The common activation of YAP in many different tumor types provides an attractive target for potential therapeutic intervention.https://doi.org/10.1186/2001-1326-3-25CancerHippo signalingYAPApoptosis |
| spellingShingle | Daniel A Barron Jacob D Kagey The role of the Hippo pathway in human disease and tumorigenesis Clinical and Translational Medicine Cancer Hippo signaling YAP Apoptosis |
| title | The role of the Hippo pathway in human disease and tumorigenesis |
| title_full | The role of the Hippo pathway in human disease and tumorigenesis |
| title_fullStr | The role of the Hippo pathway in human disease and tumorigenesis |
| title_full_unstemmed | The role of the Hippo pathway in human disease and tumorigenesis |
| title_short | The role of the Hippo pathway in human disease and tumorigenesis |
| title_sort | role of the hippo pathway in human disease and tumorigenesis |
| topic | Cancer Hippo signaling YAP Apoptosis |
| url | https://doi.org/10.1186/2001-1326-3-25 |
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