Human endogenous retrovirus type K promotes proliferation and confers sensitivity to anti-retroviral drugs in Merlin-negative schwannoma and meningioma.
dc.contributor.author | Maze, EA | |
dc.contributor.author | Agit, B | |
dc.contributor.author | Reeves, S | |
dc.contributor.author | Hilton, DA | |
dc.contributor.author | Parkinson, David | |
dc.contributor.author | Laraba, Liyam | |
dc.contributor.author | Ercolano, E | |
dc.contributor.author | Kurian, KM | |
dc.contributor.author | Hanemann, Clemens Oliver | |
dc.contributor.author | Belshaw, Robert | |
dc.contributor.author | Ammoun, Sylwia | |
dc.date.accessioned | 2021-12-22T10:42:53Z | |
dc.date.issued | 2021-12-01 | |
dc.identifier.issn | 0008-5472 | |
dc.identifier.issn | 1538-7445 | |
dc.identifier.other | canres.3857.2020 | |
dc.identifier.uri | http://hdl.handle.net/10026.1/18487 | |
dc.description.abstract |
<jats:title>Abstract</jats:title> <jats:sec> <jats:title /> <jats:p>Deficiency of the tumor suppressor Merlin causes development of schwannoma, meningioma, and ependymoma tumors, which can occur spontaneously or in the hereditary disease neurofibromatosis type 2 (NF2). Merlin mutations are also relevant in a variety of other tumors. Surgery and radiotherapy are current first-line treatments; however, tumors frequently recur with limited treatment options. Here, we use human Merlin-negative schwannoma and meningioma primary cells to investigate the involvement of the endogenous retrovirus HERV-K in tumor development. HERV-K proteins previously implicated in tumorigenesis were overexpressed in schwannoma and all meningioma grades, and disease-associated CRL4DCAF1 and YAP/TEAD pathways were implicated in this overexpression. In normal Schwann cells, ectopic overexpression of HERV-K Env increased proliferation and upregulated expression of c-Jun and pERK1/2, which are key components of known tumorigenic pathways in schwannoma, JNK/c-Jun, and RAS/RAF/MEK/ERK. Furthermore, FDA-approved retroviral protease inhibitors ritonavir, atazanavir, and lopinavir reduced proliferation of schwannoma and grade I meningioma cells. These results identify HERV-K as a critical regulator of progression in Merlin-deficient tumors and offer potential strategies for therapeutic intervention.</jats:p> </jats:sec> <jats:sec> <jats:title>Significance:</jats:title> <jats:p>The endogenous retrovirus HERV-K activates oncogenic signaling pathways and promotes proliferation of Merlin-deficient schwannomas and meningiomas, which can be targeted with antiretroviral drugs and TEAD inhibitors.</jats:p> </jats:sec> | |
dc.format.extent | 235-247 | |
dc.format.medium | Print-Electronic | |
dc.language | en | |
dc.language.iso | en | |
dc.publisher | American Association for Cancer Research (AACR) | |
dc.subject | Anti-Retroviral Agents | |
dc.subject | Carcinogenesis | |
dc.subject | Cell Proliferation | |
dc.subject | Endogenous Retroviruses | |
dc.subject | HEK293 Cells | |
dc.subject | Humans | |
dc.subject | Meningeal Neoplasms | |
dc.subject | Meningioma | |
dc.subject | Neurilemmoma | |
dc.subject | Neurofibromatosis 2 | |
dc.subject | Neurofibromin 2 | |
dc.subject | Signal Transduction | |
dc.subject | Transfection | |
dc.subject | Viral Proteins | |
dc.title | Human endogenous retrovirus type K promotes proliferation and confers sensitivity to anti-retroviral drugs in Merlin-negative schwannoma and meningioma. | |
dc.type | journal-article | |
dc.type | Journal Article | |
dc.type | Research Support, Non-U.S. Gov't | |
plymouth.author-url | https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000745025000001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=11bb513d99f797142bcfeffcc58ea008 | |
plymouth.issue | 2 | |
plymouth.volume | 82 | |
plymouth.publication-status | Published | |
plymouth.journal | Cancer Research | |
dc.identifier.doi | 10.1158/0008-5472.can-20-3857 | |
plymouth.organisational-group | /Plymouth | |
plymouth.organisational-group | /Plymouth/Faculty of Health | |
plymouth.organisational-group | /Plymouth/Faculty of Health/Peninsula Medical School | |
plymouth.organisational-group | /Plymouth/REF 2021 Researchers by UoA | |
plymouth.organisational-group | /Plymouth/REF 2021 Researchers by UoA/UoA01 Clinical Medicine | |
plymouth.organisational-group | /Plymouth/REF 2021 Researchers by UoA/UoA01 Clinical Medicine/UoA01 Clinical Medicine | |
plymouth.organisational-group | /Plymouth/Research Groups | |
plymouth.organisational-group | /Plymouth/Research Groups/Institute of Translational and Stratified Medicine (ITSMED) | |
plymouth.organisational-group | /Plymouth/Research Groups/Institute of Translational and Stratified Medicine (ITSMED)/CBR | |
plymouth.organisational-group | /Plymouth/Users by role | |
plymouth.organisational-group | /Plymouth/Users by role/Academics | |
plymouth.organisational-group | /Plymouth/Users by role/Researchers in ResearchFish submission | |
dc.publisher.place | United States | |
dcterms.dateAccepted | 2021-11-15 | |
dc.rights.embargodate | 2022-12-1 | |
dc.identifier.eissn | 1538-7445 | |
dc.rights.embargoperiod | Not known | |
rioxxterms.versionofrecord | 10.1158/0008-5472.can-20-3857 | |
rioxxterms.licenseref.uri | http://www.rioxx.net/licenses/all-rights-reserved | |
rioxxterms.licenseref.startdate | 2021-12-01 | |
rioxxterms.type | Journal Article/Review |