Genomic Hippo Pathway Alterations and Persistent YAP/TAZ Activation: New Hallmarks in Head and Neck Cancer
Head and neck squamous cell carcinoma (HNSCC) represents a highly prevalent and deadly malignancy worldwide. The prognosis for locoregionally advanced HNSCC has not appreciably improved over the past 30 years despite advances in surgical, radiation, and targeted therapies and less than 20% of HNSCC...
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MDPI AG
2022-04-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/11/8/1370 |
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| author | Farhoud Faraji Sydney I. Ramirez Paola Y. Anguiano Quiroz Amaya N. Mendez-Molina J. Silvio Gutkind |
| author_facet | Farhoud Faraji Sydney I. Ramirez Paola Y. Anguiano Quiroz Amaya N. Mendez-Molina J. Silvio Gutkind |
| author_sort | Farhoud Faraji |
| collection | DOAJ |
| description | Head and neck squamous cell carcinoma (HNSCC) represents a highly prevalent and deadly malignancy worldwide. The prognosis for locoregionally advanced HNSCC has not appreciably improved over the past 30 years despite advances in surgical, radiation, and targeted therapies and less than 20% of HNSCC patients respond to recently approved immune checkpoint inhibitors. The Hippo signaling pathway, originally discovered as a mechanism regulating tissue growth and organ size, transduces intracellular and extracellular signals to regulate the transcriptional co-activators YAP and TAZ. Alterations in the Hippo pathway resulting in persistent YAP and TAZ activation have emerged as major oncogenic drivers. Our analysis of the human HNSCC oncogenome revealed multiple genomic alterations impairing Hippo signaling and activating YAP and TAZ, which in turn contribute to HNSCC development. This includes mutations and deletions of the FAT1 gene (29%) and amplification of the WWTR1 (encoding TAZ, 14%) and YAP1 genes (8%), together representing one of the most genetically altered signaling mechanisms in this malignancy. Here, we discuss key elements of the mammalian Hippo pathway, detail mechanisms by which perturbations in Hippo signaling promote HNSCC initiation and progression and outline emerging strategies to target Hippo signaling vulnerabilities as part of novel multimodal precision therapies for HNSCC. |
| first_indexed | 2024-03-09T11:01:07Z |
| format | Article |
| id | doaj.art-6084dcc7435d41449fa47f5f8d4de50b |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T11:01:07Z |
| publishDate | 2022-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-6084dcc7435d41449fa47f5f8d4de50b2023-12-01T01:15:48ZengMDPI AGCells2073-44092022-04-01118137010.3390/cells11081370Genomic Hippo Pathway Alterations and Persistent YAP/TAZ Activation: New Hallmarks in Head and Neck CancerFarhoud Faraji0Sydney I. Ramirez1Paola Y. Anguiano Quiroz2Amaya N. Mendez-Molina3J. Silvio Gutkind4Department of Otolaryngology-Head and Neck Surgery, University of California San Diego Health, La Jolla, CA 92093, USADepartment of Pharmacology, Moores Cancer Center, University of California San Diego, La Jolla, CA 92093, USAJohn Muir College, University of California San Diego, La Jolla, CA 92093, USAEleanor Roosevelt College, University of California San Diego, La Jolla, CA 92093, USAGleiberman Head and Neck Cancer Center, University of California San Diego Health, La Jolla, CA 92093, USAHead and neck squamous cell carcinoma (HNSCC) represents a highly prevalent and deadly malignancy worldwide. The prognosis for locoregionally advanced HNSCC has not appreciably improved over the past 30 years despite advances in surgical, radiation, and targeted therapies and less than 20% of HNSCC patients respond to recently approved immune checkpoint inhibitors. The Hippo signaling pathway, originally discovered as a mechanism regulating tissue growth and organ size, transduces intracellular and extracellular signals to regulate the transcriptional co-activators YAP and TAZ. Alterations in the Hippo pathway resulting in persistent YAP and TAZ activation have emerged as major oncogenic drivers. Our analysis of the human HNSCC oncogenome revealed multiple genomic alterations impairing Hippo signaling and activating YAP and TAZ, which in turn contribute to HNSCC development. This includes mutations and deletions of the FAT1 gene (29%) and amplification of the WWTR1 (encoding TAZ, 14%) and YAP1 genes (8%), together representing one of the most genetically altered signaling mechanisms in this malignancy. Here, we discuss key elements of the mammalian Hippo pathway, detail mechanisms by which perturbations in Hippo signaling promote HNSCC initiation and progression and outline emerging strategies to target Hippo signaling vulnerabilities as part of novel multimodal precision therapies for HNSCC.https://www.mdpi.com/2073-4409/11/8/1370head and neck squamous cell carcinomaHNSCHNSCCHippoYAPTAZ |
| spellingShingle | Farhoud Faraji Sydney I. Ramirez Paola Y. Anguiano Quiroz Amaya N. Mendez-Molina J. Silvio Gutkind Genomic Hippo Pathway Alterations and Persistent YAP/TAZ Activation: New Hallmarks in Head and Neck Cancer Cells head and neck squamous cell carcinoma HNSC HNSCC Hippo YAP TAZ |
| title | Genomic Hippo Pathway Alterations and Persistent YAP/TAZ Activation: New Hallmarks in Head and Neck Cancer |
| title_full | Genomic Hippo Pathway Alterations and Persistent YAP/TAZ Activation: New Hallmarks in Head and Neck Cancer |
| title_fullStr | Genomic Hippo Pathway Alterations and Persistent YAP/TAZ Activation: New Hallmarks in Head and Neck Cancer |
| title_full_unstemmed | Genomic Hippo Pathway Alterations and Persistent YAP/TAZ Activation: New Hallmarks in Head and Neck Cancer |
| title_short | Genomic Hippo Pathway Alterations and Persistent YAP/TAZ Activation: New Hallmarks in Head and Neck Cancer |
| title_sort | genomic hippo pathway alterations and persistent yap taz activation new hallmarks in head and neck cancer |
| topic | head and neck squamous cell carcinoma HNSC HNSCC Hippo YAP TAZ |
| url | https://www.mdpi.com/2073-4409/11/8/1370 |
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