Drug Vulnerabilities and Disease Prognosis Linked to the Stem Cell-Like Gene Expression Program Triggered by the RHO GTPase Activator VAV2 in Hyperplastic Keratinocytes and Head and Neck Cancer

© 2020 by the authors.

Bibliographic Details
Authors: Lorenzo-Martín, L. Francisco, Menacho-Márquez, Mauricio, Bustelo, Xosé R.
Format: article
Status:Published version
Publication Date:2020
Country:España
Institution:Consejo Superior de Investigaciones Científicas (CSIC)
Repository:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/230746
Online Access:http://hdl.handle.net/10261/230746
Access Level:Open access
Keyword:VAV2
VAV family
Rac1
RhoA
GTPases
Skin
Head and neck
Keratinocytes
Cancer
Oncogenes
Signaling
Regenerative proliferation
Stem cells
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spelling Drug Vulnerabilities and Disease Prognosis Linked to the Stem Cell-Like Gene Expression Program Triggered by the RHO GTPase Activator VAV2 in Hyperplastic Keratinocytes and Head and Neck CancerLorenzo-Martín, L. FranciscoMenacho-Márquez, MauricioBustelo, Xosé R.VAV2VAV familyRac1RhoAGTPasesSkinHead and neckKeratinocytesCancerOncogenesSignalingRegenerative proliferationStem cells© 2020 by the authors.We have recently shown that VAV2, a guanosine nucleotide exchange factor that catalyzes the stimulation step of RHO GTPases, is involved in a stem cell-like (SCL) regenerative proliferation program that is important for the development and subsequent maintenance of the tumorigenesis of both cutaneous (cSCC) and head and neck squamous cell carcinomas (hnSCC). In line with this, we have observed that the levels of the VAV2 mRNA and VAV2-regulated gene signatures are associated with poor prognosis in the case of human papillomavirus-negative hnSCC patients. These results suggest that the SCL program elicited by VAV2 in those cells can harbor therapeutically actionable downstream targets. We have addressed this issue using a combination of both in silico and wet-lab approaches. Here, we show that the VAV2-regulated SCL program does harbor a number of cell cycle- and signaling-related kinases that are essential for the viability of undifferentiated keratinocytes and hnSCC patient-derived cells endowed with high levels of VAV2 activity. Our results also show that the VAV2-regulated SCL gene signature is associated with poor hnSCC patient prognosis. Collectively, these data underscore the critical role of this VAV2-regulated SCL program for the viability of both preneoplastic and fully transformed keratinocytes.X.R.B. is supported by grants from Worldwide Cancer Research (14-1248), the Castilla-León Government (CSI049U16, CLC-2017-01), the Spanish Ministry of Science and Innovation (RTI2018-096481-B-I00) and the Spanish Association against Cancer (GC16173472GARC). X.R.B.’s institution is supported by the Programa de Apoyo a Planes Estratégicos de Investigación de Estructuras de Investigación de Excelencia of the Ministry of Education of the Castilla-León Government (CLC-2017-01). L.F.L.-M. has been supported by funding from the Spanish Ministry of Education, Culture and Sports (L.F.L.-M., FPU13/02923) and the CLC-2017-01 grant. Both Spanish and Castilla-León government-associated funding is partially supported by the European Regional Development Fund.Multidisciplinary Digital Publishing InstituteWorldwide Cancer ResearchJunta de Castilla y LeónMinisterio de Ciencia e Innovación (España)Agencia Estatal de Investigación (España)Asociación Española Contra el CáncerMinisterio de Educación, Cultura y Deporte (España)European CommissionConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2021202120202021info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/230746reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/RTI2018-096481-B-I00RTI2018-096481-B-I00/AEI/10.13039/501100011033http://dx.doi.org/10.3390/cancers12092498Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/2307462026-05-22T06:33:51Z
dc.title.none.fl_str_mv Drug Vulnerabilities and Disease Prognosis Linked to the Stem Cell-Like Gene Expression Program Triggered by the RHO GTPase Activator VAV2 in Hyperplastic Keratinocytes and Head and Neck Cancer
title Drug Vulnerabilities and Disease Prognosis Linked to the Stem Cell-Like Gene Expression Program Triggered by the RHO GTPase Activator VAV2 in Hyperplastic Keratinocytes and Head and Neck Cancer
spellingShingle Drug Vulnerabilities and Disease Prognosis Linked to the Stem Cell-Like Gene Expression Program Triggered by the RHO GTPase Activator VAV2 in Hyperplastic Keratinocytes and Head and Neck Cancer
Lorenzo-Martín, L. Francisco
VAV2
VAV family
Rac1
RhoA
GTPases
Skin
Head and neck
Keratinocytes
Cancer
Oncogenes
Signaling
Regenerative proliferation
Stem cells
title_short Drug Vulnerabilities and Disease Prognosis Linked to the Stem Cell-Like Gene Expression Program Triggered by the RHO GTPase Activator VAV2 in Hyperplastic Keratinocytes and Head and Neck Cancer
title_full Drug Vulnerabilities and Disease Prognosis Linked to the Stem Cell-Like Gene Expression Program Triggered by the RHO GTPase Activator VAV2 in Hyperplastic Keratinocytes and Head and Neck Cancer
title_fullStr Drug Vulnerabilities and Disease Prognosis Linked to the Stem Cell-Like Gene Expression Program Triggered by the RHO GTPase Activator VAV2 in Hyperplastic Keratinocytes and Head and Neck Cancer
title_full_unstemmed Drug Vulnerabilities and Disease Prognosis Linked to the Stem Cell-Like Gene Expression Program Triggered by the RHO GTPase Activator VAV2 in Hyperplastic Keratinocytes and Head and Neck Cancer
title_sort Drug Vulnerabilities and Disease Prognosis Linked to the Stem Cell-Like Gene Expression Program Triggered by the RHO GTPase Activator VAV2 in Hyperplastic Keratinocytes and Head and Neck Cancer
dc.creator.none.fl_str_mv Lorenzo-Martín, L. Francisco
Menacho-Márquez, Mauricio
Bustelo, Xosé R.
author Lorenzo-Martín, L. Francisco
author_facet Lorenzo-Martín, L. Francisco
Menacho-Márquez, Mauricio
Bustelo, Xosé R.
author_role author
author2 Menacho-Márquez, Mauricio
Bustelo, Xosé R.
author2_role author
author
dc.contributor.none.fl_str_mv Worldwide Cancer Research
Junta de Castilla y León
Ministerio de Ciencia e Innovación (España)
Agencia Estatal de Investigación (España)
Asociación Española Contra el Cáncer
Ministerio de Educación, Cultura y Deporte (España)
European Commission
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv VAV2
VAV family
Rac1
RhoA
GTPases
Skin
Head and neck
Keratinocytes
Cancer
Oncogenes
Signaling
Regenerative proliferation
Stem cells
topic VAV2
VAV family
Rac1
RhoA
GTPases
Skin
Head and neck
Keratinocytes
Cancer
Oncogenes
Signaling
Regenerative proliferation
Stem cells
description © 2020 by the authors.
publishDate 2020
dc.date.none.fl_str_mv 2020
2021
2021
2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/230746
url http://hdl.handle.net/10261/230746
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/RTI2018-096481-B-I00
RTI2018-096481-B-I00/AEI/10.13039/501100011033
http://dx.doi.org/10.3390/cancers12092498
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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