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
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/145681
Ver los metadatos del registro completo
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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 Técnicas2025-09-29T10:46:00Zoai: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:34982025-09-29 10:46:00.813CONICET 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 |
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1844614500524752896 |
score |
13.070432 |