ROR2 has a protective role in melanoma by inhibiting Akt activity, cell-cycle progression, and proliferation

Autores
Castro, María Victoria; Barbero, Gastón Alexis; Villanueva, María Belén; Grumolato, Luca; Nsengimana, Jérémie; Newton-Bishop, Julia; Illescas, Edith; Quezada, Maria Josefina; Lopez Bergami, Pablo Roberto
Año de publicación
2021
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Background: Receptor tyrosine kinase-like orphan receptor 2 (ROR2) is a Wnt5a receptor aberrantly expressed in cancer that was shown to either suppress or promote carcinogenesis in different tumor types. Our goal was to study the role of ROR2 in melanoma. Methods: Gain and loss-of-function strategies were applied to study the biological function of ROR2 in melanoma. Proliferation assays, flow cytometry, and western blotting were used to evaluate cell proliferation and changes in expression levels of cell-cycle and proliferation markers. The role of ROR2 in tumor growth was assessed in xenotransplantation experiments followed by immunohistochemistry analysis of the tumors. The role of ROR2 in melanoma patients was assessed by analysis of clinical data from the Leeds Melanoma Cohort. Results: Unlike previous findings describing ROR2 as an oncogene in melanoma, we describe that ROR2 prevents tumor growth by inhibiting cell-cycle progression and the proliferation of melanoma cells. The effect of ROR2 is mediated by inhibition of Akt phosphorylation and activity which, in turn, regulates the expression, phosphorylation, and localization of major cell-cycle regulators including cyclins (A, B, D, and E), CDK1, CDK4, RB, p21, and p27. Xenotransplantation experiments demonstrated that ROR2 also reduces proliferation in vivo, resulting in inhibition of tumor growth. In agreement with these findings, a higher ROR2 level favors thin and non-ulcerated primary melanomas with reduced mitotic rate and better prognosis. Conclusion: We conclude that the expression of ROR2 slows down the growth of primary tumors and contributes to prolonging melanoma survival. Our results demonstrate that ROR2 has a far more complex role than originally described.
Fil: Castro, María Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Maimónides. Área de Investigaciones Biomédicas y Biotecnológicas. Centro de Estudios Biomédicos, Biotecnológicos, Ambientales y de Diagnóstico; Argentina
Fil: Barbero, Gastón Alexis. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Maimónides. Área de Investigaciones Biomédicas y Biotecnológicas. Centro de Estudios Biomédicos, Biotecnológicos, Ambientales y de Diagnóstico; Argentina
Fil: Villanueva, María Belén. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Maimónides. Área de Investigaciones Biomédicas y Biotecnológicas. Centro de Estudios Biomédicos, Biotecnológicos, Ambientales y de Diagnóstico; Argentina
Fil: Grumolato, Luca. University of Rouen; Francia
Fil: Nsengimana, Jérémie. University of Newcastle; Reino Unido
Fil: Newton-Bishop, Julia. Leeds Institute Of Medical Research; Reino Unido
Fil: Illescas, Edith. Universidad Maimónides. Área de Investigaciones Biomédicas y Biotecnológicas. Centro de Estudios Biomédicos, Biotecnológicos, Ambientales y de Diagnóstico; Argentina
Fil: Quezada, Maria Josefina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Maimónides. Área de Investigaciones Biomédicas y Biotecnológicas. Centro de Estudios Biomédicos, Biotecnológicos, Ambientales y de Diagnóstico; Argentina
Fil: Lopez Bergami, Pablo Roberto. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Maimónides. Área de Investigaciones Biomédicas y Biotecnológicas. Centro de Estudios Biomédicos, Biotecnológicos, Ambientales y de Diagnóstico; Argentina
Materia
AKT
BRESLOW THICKNESS
CELL-CYCLE
CYCLINS
MELANOMA
PROLIFERATION
ROR2
SURVIVAL
WNT5A
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/166496
Acceder
id CONICETDig_e00bbd70a5877ed7f2267781059c2afb
oai_identifier_str oai:ri.conicet.gov.ar:11336/166496
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling ROR2 has a protective role in melanoma by inhibiting Akt activity, cell-cycle progression, and proliferationCastro, María VictoriaBarbero, Gastón AlexisVillanueva, María BelénGrumolato, LucaNsengimana, JérémieNewton-Bishop, JuliaIllescas, EdithQuezada, Maria JosefinaLopez Bergami, Pablo RobertoAKTBRESLOW THICKNESSCELL-CYCLECYCLINSMELANOMAPROLIFERATIONROR2SURVIVALWNT5Ahttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Background: Receptor tyrosine kinase-like orphan receptor 2 (ROR2) is a Wnt5a receptor aberrantly expressed in cancer that was shown to either suppress or promote carcinogenesis in different tumor types. Our goal was to study the role of ROR2 in melanoma. Methods: Gain and loss-of-function strategies were applied to study the biological function of ROR2 in melanoma. Proliferation assays, flow cytometry, and western blotting were used to evaluate cell proliferation and changes in expression levels of cell-cycle and proliferation markers. The role of ROR2 in tumor growth was assessed in xenotransplantation experiments followed by immunohistochemistry analysis of the tumors. The role of ROR2 in melanoma patients was assessed by analysis of clinical data from the Leeds Melanoma Cohort. Results: Unlike previous findings describing ROR2 as an oncogene in melanoma, we describe that ROR2 prevents tumor growth by inhibiting cell-cycle progression and the proliferation of melanoma cells. The effect of ROR2 is mediated by inhibition of Akt phosphorylation and activity which, in turn, regulates the expression, phosphorylation, and localization of major cell-cycle regulators including cyclins (A, B, D, and E), CDK1, CDK4, RB, p21, and p27. Xenotransplantation experiments demonstrated that ROR2 also reduces proliferation in vivo, resulting in inhibition of tumor growth. In agreement with these findings, a higher ROR2 level favors thin and non-ulcerated primary melanomas with reduced mitotic rate and better prognosis. Conclusion: We conclude that the expression of ROR2 slows down the growth of primary tumors and contributes to prolonging melanoma survival. Our results demonstrate that ROR2 has a far more complex role than originally described.Fil: Castro, María Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Maimónides. Área de Investigaciones Biomédicas y Biotecnológicas. Centro de Estudios Biomédicos, Biotecnológicos, Ambientales y de Diagnóstico; ArgentinaFil: Barbero, Gastón Alexis. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Maimónides. Área de Investigaciones Biomédicas y Biotecnológicas. Centro de Estudios Biomédicos, Biotecnológicos, Ambientales y de Diagnóstico; ArgentinaFil: Villanueva, María Belén. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Maimónides. Área de Investigaciones Biomédicas y Biotecnológicas. Centro de Estudios Biomédicos, Biotecnológicos, Ambientales y de Diagnóstico; ArgentinaFil: Grumolato, Luca. University of Rouen; FranciaFil: Nsengimana, Jérémie. University of Newcastle; Reino UnidoFil: Newton-Bishop, Julia. Leeds Institute Of Medical Research; Reino UnidoFil: Illescas, Edith. Universidad Maimónides. Área de Investigaciones Biomédicas y Biotecnológicas. Centro de Estudios Biomédicos, Biotecnológicos, Ambientales y de Diagnóstico; ArgentinaFil: Quezada, Maria Josefina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Maimónides. Área de Investigaciones Biomédicas y Biotecnológicas. Centro de Estudios Biomédicos, Biotecnológicos, Ambientales y de Diagnóstico; ArgentinaFil: Lopez Bergami, Pablo Roberto. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Maimónides. Área de Investigaciones Biomédicas y Biotecnológicas. Centro de Estudios Biomédicos, Biotecnológicos, Ambientales y de Diagnóstico; ArgentinaBioMed Central2021-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/166496Castro, María Victoria; Barbero, Gastón Alexis; Villanueva, María Belén; Grumolato, Luca; Nsengimana, Jérémie; et al.; ROR2 has a protective role in melanoma by inhibiting Akt activity, cell-cycle progression, and proliferation; BioMed Central; Journal Of Biomedical Science; 28; 1; 12-2021; 1-151423-0127CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://jbiomedsci.biomedcentral.com/articles/10.1186/s12929-021-00776-winfo:eu-repo/semantics/altIdentifier/doi/10.1186/s12929-021-00776-winfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:00:13Zoai:ri.conicet.gov.ar:11336/166496instacron: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:34982025-09-03 10:00:13.481CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv ROR2 has a protective role in melanoma by inhibiting Akt activity, cell-cycle progression, and proliferation
title ROR2 has a protective role in melanoma by inhibiting Akt activity, cell-cycle progression, and proliferation
spellingShingle ROR2 has a protective role in melanoma by inhibiting Akt activity, cell-cycle progression, and proliferation
Castro, María Victoria
AKT
BRESLOW THICKNESS
CELL-CYCLE
CYCLINS
MELANOMA
PROLIFERATION
ROR2
SURVIVAL
WNT5A
title_short ROR2 has a protective role in melanoma by inhibiting Akt activity, cell-cycle progression, and proliferation
title_full ROR2 has a protective role in melanoma by inhibiting Akt activity, cell-cycle progression, and proliferation
title_fullStr ROR2 has a protective role in melanoma by inhibiting Akt activity, cell-cycle progression, and proliferation
title_full_unstemmed ROR2 has a protective role in melanoma by inhibiting Akt activity, cell-cycle progression, and proliferation
title_sort ROR2 has a protective role in melanoma by inhibiting Akt activity, cell-cycle progression, and proliferation
dc.creator.none.fl_str_mv Castro, María Victoria
Barbero, Gastón Alexis
Villanueva, María Belén
Grumolato, Luca
Nsengimana, Jérémie
Newton-Bishop, Julia
Illescas, Edith
Quezada, Maria Josefina
Lopez Bergami, Pablo Roberto
author Castro, María Victoria
author_facet Castro, María Victoria
Barbero, Gastón Alexis
Villanueva, María Belén
Grumolato, Luca
Nsengimana, Jérémie
Newton-Bishop, Julia
Illescas, Edith
Quezada, Maria Josefina
Lopez Bergami, Pablo Roberto
author_role author
author2 Barbero, Gastón Alexis
Villanueva, María Belén
Grumolato, Luca
Nsengimana, Jérémie
Newton-Bishop, Julia
Illescas, Edith
Quezada, Maria Josefina
Lopez Bergami, Pablo Roberto
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv AKT
BRESLOW THICKNESS
CELL-CYCLE
CYCLINS
MELANOMA
PROLIFERATION
ROR2
SURVIVAL
WNT5A
topic AKT
BRESLOW THICKNESS
CELL-CYCLE
CYCLINS
MELANOMA
PROLIFERATION
ROR2
SURVIVAL
WNT5A
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Background: Receptor tyrosine kinase-like orphan receptor 2 (ROR2) is a Wnt5a receptor aberrantly expressed in cancer that was shown to either suppress or promote carcinogenesis in different tumor types. Our goal was to study the role of ROR2 in melanoma. Methods: Gain and loss-of-function strategies were applied to study the biological function of ROR2 in melanoma. Proliferation assays, flow cytometry, and western blotting were used to evaluate cell proliferation and changes in expression levels of cell-cycle and proliferation markers. The role of ROR2 in tumor growth was assessed in xenotransplantation experiments followed by immunohistochemistry analysis of the tumors. The role of ROR2 in melanoma patients was assessed by analysis of clinical data from the Leeds Melanoma Cohort. Results: Unlike previous findings describing ROR2 as an oncogene in melanoma, we describe that ROR2 prevents tumor growth by inhibiting cell-cycle progression and the proliferation of melanoma cells. The effect of ROR2 is mediated by inhibition of Akt phosphorylation and activity which, in turn, regulates the expression, phosphorylation, and localization of major cell-cycle regulators including cyclins (A, B, D, and E), CDK1, CDK4, RB, p21, and p27. Xenotransplantation experiments demonstrated that ROR2 also reduces proliferation in vivo, resulting in inhibition of tumor growth. In agreement with these findings, a higher ROR2 level favors thin and non-ulcerated primary melanomas with reduced mitotic rate and better prognosis. Conclusion: We conclude that the expression of ROR2 slows down the growth of primary tumors and contributes to prolonging melanoma survival. Our results demonstrate that ROR2 has a far more complex role than originally described.
Fil: Castro, María Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Maimónides. Área de Investigaciones Biomédicas y Biotecnológicas. Centro de Estudios Biomédicos, Biotecnológicos, Ambientales y de Diagnóstico; Argentina
Fil: Barbero, Gastón Alexis. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Maimónides. Área de Investigaciones Biomédicas y Biotecnológicas. Centro de Estudios Biomédicos, Biotecnológicos, Ambientales y de Diagnóstico; Argentina
Fil: Villanueva, María Belén. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Maimónides. Área de Investigaciones Biomédicas y Biotecnológicas. Centro de Estudios Biomédicos, Biotecnológicos, Ambientales y de Diagnóstico; Argentina
Fil: Grumolato, Luca. University of Rouen; Francia
Fil: Nsengimana, Jérémie. University of Newcastle; Reino Unido
Fil: Newton-Bishop, Julia. Leeds Institute Of Medical Research; Reino Unido
Fil: Illescas, Edith. Universidad Maimónides. Área de Investigaciones Biomédicas y Biotecnológicas. Centro de Estudios Biomédicos, Biotecnológicos, Ambientales y de Diagnóstico; Argentina
Fil: Quezada, Maria Josefina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Maimónides. Área de Investigaciones Biomédicas y Biotecnológicas. Centro de Estudios Biomédicos, Biotecnológicos, Ambientales y de Diagnóstico; Argentina
Fil: Lopez Bergami, Pablo Roberto. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Maimónides. Área de Investigaciones Biomédicas y Biotecnológicas. Centro de Estudios Biomédicos, Biotecnológicos, Ambientales y de Diagnóstico; Argentina
description Background: Receptor tyrosine kinase-like orphan receptor 2 (ROR2) is a Wnt5a receptor aberrantly expressed in cancer that was shown to either suppress or promote carcinogenesis in different tumor types. Our goal was to study the role of ROR2 in melanoma. Methods: Gain and loss-of-function strategies were applied to study the biological function of ROR2 in melanoma. Proliferation assays, flow cytometry, and western blotting were used to evaluate cell proliferation and changes in expression levels of cell-cycle and proliferation markers. The role of ROR2 in tumor growth was assessed in xenotransplantation experiments followed by immunohistochemistry analysis of the tumors. The role of ROR2 in melanoma patients was assessed by analysis of clinical data from the Leeds Melanoma Cohort. Results: Unlike previous findings describing ROR2 as an oncogene in melanoma, we describe that ROR2 prevents tumor growth by inhibiting cell-cycle progression and the proliferation of melanoma cells. The effect of ROR2 is mediated by inhibition of Akt phosphorylation and activity which, in turn, regulates the expression, phosphorylation, and localization of major cell-cycle regulators including cyclins (A, B, D, and E), CDK1, CDK4, RB, p21, and p27. Xenotransplantation experiments demonstrated that ROR2 also reduces proliferation in vivo, resulting in inhibition of tumor growth. In agreement with these findings, a higher ROR2 level favors thin and non-ulcerated primary melanomas with reduced mitotic rate and better prognosis. Conclusion: We conclude that the expression of ROR2 slows down the growth of primary tumors and contributes to prolonging melanoma survival. Our results demonstrate that ROR2 has a far more complex role than originally described.
publishDate 2021
dc.date.none.fl_str_mv 2021-12
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/11336/166496
Castro, María Victoria; Barbero, Gastón Alexis; Villanueva, María Belén; Grumolato, Luca; Nsengimana, Jérémie; et al.; ROR2 has a protective role in melanoma by inhibiting Akt activity, cell-cycle progression, and proliferation; BioMed Central; Journal Of Biomedical Science; 28; 1; 12-2021; 1-15
1423-0127
CONICET Digital
CONICET
url http://hdl.handle.net/11336/166496
identifier_str_mv Castro, María Victoria; Barbero, Gastón Alexis; Villanueva, María Belén; Grumolato, Luca; Nsengimana, Jérémie; et al.; ROR2 has a protective role in melanoma by inhibiting Akt activity, cell-cycle progression, and proliferation; BioMed Central; Journal Of Biomedical Science; 28; 1; 12-2021; 1-15
1423-0127
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://jbiomedsci.biomedcentral.com/articles/10.1186/s12929-021-00776-w
info:eu-repo/semantics/altIdentifier/doi/10.1186/s12929-021-00776-w
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv BioMed Central
publisher.none.fl_str_mv BioMed Central
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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score 13.13397

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