YAP1 activation by human papillomavirus E7 promotes basal cell identity in squamous epithelia
Persistent human papillomavirus (HPV) infection of stratified squamous epithelial cells causes nearly 5% of cancer cases worldwide. HPV-positive oropharyngeal cancers harbor few mutations in the Hippo signaling pathway compared to HPV-negative cancers at the same anatomical site, prompting the hypot...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2022-02-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/75466 |
| _version_ | 1811235819621449728 |
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| author | Joshua Hatterschide Paola Castagnino Hee Won Kim Steven M Sperry Kathleen T Montone Devraj Basu Elizabeth A White |
| author_facet | Joshua Hatterschide Paola Castagnino Hee Won Kim Steven M Sperry Kathleen T Montone Devraj Basu Elizabeth A White |
| author_sort | Joshua Hatterschide |
| collection | DOAJ |
| description | Persistent human papillomavirus (HPV) infection of stratified squamous epithelial cells causes nearly 5% of cancer cases worldwide. HPV-positive oropharyngeal cancers harbor few mutations in the Hippo signaling pathway compared to HPV-negative cancers at the same anatomical site, prompting the hypothesis that an HPV-encoded protein inactivates the Hippo pathway and activates the Hippo effector yes-associated protein (YAP1). The HPV E7 oncoprotein is required for HPV infection and for HPV-mediated oncogenic transformation. We investigated the effects of HPV oncoproteins on YAP1 and found that E7 activates YAP1, promoting YAP1 nuclear localization in basal epithelial cells. YAP1 activation by HPV E7 required that E7 binds and degrades the tumor suppressor protein tyrosine phosphatase non-receptor type 14 (PTPN14). E7 required YAP1 transcriptional activity to extend the lifespan of primary keratinocytes, indicating that YAP1 activation contributes to E7 carcinogenic activity. Maintaining infection in basal cells is critical for HPV persistence, and here we demonstrate that YAP1 activation causes HPV E7 expressing cells to be retained in the basal compartment of stratified epithelia. We propose that YAP1 activation resulting from PTPN14 inactivation is an essential, targetable activity of the HPV E7 oncoprotein relevant to HPV infection and carcinogenesis. |
| first_indexed | 2024-04-12T11:58:32Z |
| format | Article |
| id | doaj.art-cba4083c22774cf3ae057bc2d8774083 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T11:58:32Z |
| publishDate | 2022-02-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-cba4083c22774cf3ae057bc2d87740832022-12-22T03:33:56ZengeLife Sciences Publications LtdeLife2050-084X2022-02-011110.7554/eLife.75466YAP1 activation by human papillomavirus E7 promotes basal cell identity in squamous epitheliaJoshua Hatterschide0https://orcid.org/0000-0003-3562-4166Paola Castagnino1Hee Won Kim2https://orcid.org/0000-0001-5642-0969Steven M Sperry3Kathleen T Montone4Devraj Basu5Elizabeth A White6https://orcid.org/0000-0001-7378-7690Department of Otorhinolaryngology: Head and Neck Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, United StatesDepartment of Otorhinolaryngology: Head and Neck Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, United StatesDepartment of Otorhinolaryngology: Head and Neck Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, United StatesDepartment of Otorhinolaryngology: Head and Neck Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, United StatesDepartment of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, United StatesDepartment of Otorhinolaryngology: Head and Neck Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, United StatesDepartment of Otorhinolaryngology: Head and Neck Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, United StatesPersistent human papillomavirus (HPV) infection of stratified squamous epithelial cells causes nearly 5% of cancer cases worldwide. HPV-positive oropharyngeal cancers harbor few mutations in the Hippo signaling pathway compared to HPV-negative cancers at the same anatomical site, prompting the hypothesis that an HPV-encoded protein inactivates the Hippo pathway and activates the Hippo effector yes-associated protein (YAP1). The HPV E7 oncoprotein is required for HPV infection and for HPV-mediated oncogenic transformation. We investigated the effects of HPV oncoproteins on YAP1 and found that E7 activates YAP1, promoting YAP1 nuclear localization in basal epithelial cells. YAP1 activation by HPV E7 required that E7 binds and degrades the tumor suppressor protein tyrosine phosphatase non-receptor type 14 (PTPN14). E7 required YAP1 transcriptional activity to extend the lifespan of primary keratinocytes, indicating that YAP1 activation contributes to E7 carcinogenic activity. Maintaining infection in basal cells is critical for HPV persistence, and here we demonstrate that YAP1 activation causes HPV E7 expressing cells to be retained in the basal compartment of stratified epithelia. We propose that YAP1 activation resulting from PTPN14 inactivation is an essential, targetable activity of the HPV E7 oncoprotein relevant to HPV infection and carcinogenesis.https://elifesciences.org/articles/75466HPVpapillomavirusYAP1cell fatestem cellPTPN14 |
| spellingShingle | Joshua Hatterschide Paola Castagnino Hee Won Kim Steven M Sperry Kathleen T Montone Devraj Basu Elizabeth A White YAP1 activation by human papillomavirus E7 promotes basal cell identity in squamous epithelia eLife HPV papillomavirus YAP1 cell fate stem cell PTPN14 |
| title | YAP1 activation by human papillomavirus E7 promotes basal cell identity in squamous epithelia |
| title_full | YAP1 activation by human papillomavirus E7 promotes basal cell identity in squamous epithelia |
| title_fullStr | YAP1 activation by human papillomavirus E7 promotes basal cell identity in squamous epithelia |
| title_full_unstemmed | YAP1 activation by human papillomavirus E7 promotes basal cell identity in squamous epithelia |
| title_short | YAP1 activation by human papillomavirus E7 promotes basal cell identity in squamous epithelia |
| title_sort | yap1 activation by human papillomavirus e7 promotes basal cell identity in squamous epithelia |
| topic | HPV papillomavirus YAP1 cell fate stem cell PTPN14 |
| url | https://elifesciences.org/articles/75466 |
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