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 an...

Autores
Lorenzo Martín, Luis Francisco; Menacho Márquez, Mauricio Ariel; Bustelo, Xosé R.
Año de publicación
2020
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
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 cycleand 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.
Fil: Lorenzo Martín, Luis Francisco. Consejo Superior de Investigaciones Científicas; España. Universidad de Salamanca; España
Fil: Menacho Márquez, Mauricio Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Inmunología Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología Clinica y Experimental de Rosario; Argentina
Fil: Bustelo, Xosé R.. Universidad de Salamanca; España. Consejo Superior de Investigaciones Científicas; España
Materia
CANCER
GTPASES
HEAD AND NECK
KERATINOCYTES
ONCOGENES
RAC1
REGENERATIVE PROLIFERATION
RHOA
SIGNALING
SKIN
STEM CELLS
VAV FAMILY
VAV2
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/145681
Acceder
id CONICETDig_6f022ec55c64711eb13a36273d8e77d1
oai_identifier_str oai:ri.conicet.gov.ar:11336/145681
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
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, Luis FranciscoMenacho Márquez, Mauricio ArielBustelo, Xosé R.CANCERGTPASESHEAD AND NECKKERATINOCYTESONCOGENESRAC1REGENERATIVE PROLIFERATIONRHOASIGNALINGSKINSTEM CELLSVAV FAMILYVAV2https://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1We 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 cycleand 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.Fil: Lorenzo Martín, Luis Francisco. Consejo Superior de Investigaciones Científicas; España. Universidad de Salamanca; EspañaFil: Menacho Márquez, Mauricio Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Inmunología Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología Clinica y Experimental de Rosario; ArgentinaFil: Bustelo, Xosé R.. Universidad de Salamanca; España. Consejo Superior de Investigaciones Científicas; EspañaMolecular Diversity Preservation International2020-09info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/145681Lorenzo Martín, Luis Francisco; Menacho Márquez, Mauricio Ariel; Bustelo, Xosé R.; 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; Molecular Diversity Preservation International; Cancers; 12; 9; 9-2020; 1-152072-6694CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/2072-6694/12/9/2498info:eu-repo/semantics/altIdentifier/doi/10.3390/cancers12092498info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T12:19:20Zoai:ri.conicet.gov.ar:11336/145681instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-22 12:19:20.572CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
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, Luis Francisco
CANCER
GTPASES
HEAD AND NECK
KERATINOCYTES
ONCOGENES
RAC1
REGENERATIVE PROLIFERATION
RHOA
SIGNALING
SKIN
STEM CELLS
VAV FAMILY
VAV2
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, Luis Francisco
Menacho Márquez, Mauricio Ariel
Bustelo, Xosé R.
author Lorenzo Martín, Luis Francisco
author_facet Lorenzo Martín, Luis Francisco
Menacho Márquez, Mauricio Ariel
Bustelo, Xosé R.
author_role author
author2 Menacho Márquez, Mauricio Ariel
Bustelo, Xosé R.
author2_role author
author
dc.subject.none.fl_str_mv CANCER
GTPASES
HEAD AND NECK
KERATINOCYTES
ONCOGENES
RAC1
REGENERATIVE PROLIFERATION
RHOA
SIGNALING
SKIN
STEM CELLS
VAV FAMILY
VAV2
topic CANCER
GTPASES
HEAD AND NECK
KERATINOCYTES
ONCOGENES
RAC1
REGENERATIVE PROLIFERATION
RHOA
SIGNALING
SKIN
STEM CELLS
VAV FAMILY
VAV2
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv 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 cycleand 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.
Fil: Lorenzo Martín, Luis Francisco. Consejo Superior de Investigaciones Científicas; España. Universidad de Salamanca; España
Fil: Menacho Márquez, Mauricio Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Inmunología Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología Clinica y Experimental de Rosario; Argentina
Fil: Bustelo, Xosé R.. Universidad de Salamanca; España. Consejo Superior de Investigaciones Científicas; España
description 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 cycleand 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.
publishDate 2020
dc.date.none.fl_str_mv 2020-09
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/145681
Lorenzo Martín, Luis Francisco; Menacho Márquez, Mauricio Ariel; Bustelo, Xosé R.; 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; Molecular Diversity Preservation International; Cancers; 12; 9; 9-2020; 1-15
2072-6694
CONICET Digital
CONICET
url http://hdl.handle.net/11336/145681
identifier_str_mv Lorenzo Martín, Luis Francisco; Menacho Márquez, Mauricio Ariel; Bustelo, Xosé R.; 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; Molecular Diversity Preservation International; Cancers; 12; 9; 9-2020; 1-15
2072-6694
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/2072-6694/12/9/2498
info:eu-repo/semantics/altIdentifier/doi/10.3390/cancers12092498
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Molecular Diversity Preservation International
publisher.none.fl_str_mv Molecular Diversity Preservation International
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
_version_ 1846782631266484224
score 12.982451

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