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dc.contributor.author
Lopez Bergami, Pablo Roberto
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dc.contributor.author
Barbero, Gastón Alexis
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dc.date.available
2022-09-15T18:23:15Z
dc.date.issued
2020-05-20
dc.identifier.citation
Lopez Bergami, Pablo Roberto; Barbero, Gastón Alexis; The emerging role of Wnt5a in the promotion of a pro-inflammatory and immunosuppressive tumor microenvironment; Springer; Cancer And Metastasis Reviews; 39; 3; 20-5-2020; 933-952
dc.identifier.issn
0167-7659
dc.identifier.uri
http://hdl.handle.net/11336/168991
dc.description.abstract
Wnt5a is the prototypical activator of the non-canonical Wnt pathways, and its overexpression has been implicated in the progression of several tumor types by promoting cell motility, invasion, EMT, and metastasis. Recent evidences have revealed a novel role of Wnt5a in the phosphorylation of the NF-κB subunit p65 and the activation of the NF-κB pathway in cancer cells. In this article, we review the molecular mechanisms and mediators defining a Wnt5a/NF-κB signaling pathway and propose that the aberrant expression of Wnt5a in some tumors drives a Wnt5a/NF-κB/IL-6/STAT3 positive feedback loop that amplifies the effects of Wnt5a. The evidences discussed here suggest that Wnt5a has a double effect on the tumor microenvironment. First, it activates an autocrine ROR1/Akt/p65 pathway that promotes inflammation and chemotaxis of immune cells. Then, Wnt5a activates a TLR/MyD88/p50 pathway exclusively in myelomonocytic cells promoting the synthesis of the anti-inflammatory cytokine IL-10 and a tolerogenic phenotype. As a result of these mechanisms, Wnt5a plays a negative role on immune cell function that contributes to an immunosuppressive tumor microenvironment and would contribute to resistance to immunotherapy. Finally, we summarized the development of different strategies targeting either Wnt5a or the Wnt5a receptor ROR1 that can be helpful for cancer therapy by contributing to generate a more immunostimulatory tumor microenvironment.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Springer
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dc.rights
info:eu-repo/semantics/restrictedAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
AKT
dc.subject
CYTOKINE
dc.subject
IMMUNOTHERAPY
dc.subject
NF-ΚB
dc.subject
ROR1
dc.subject
WNT5A
dc.subject.classification
Bioquímica y Biología Molecular
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dc.subject.classification
Ciencias Biológicas
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dc.subject.classification
CIENCIAS NATURALES Y EXACTAS
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dc.title
The emerging role of Wnt5a in the promotion of a pro-inflammatory and immunosuppressive tumor microenvironment
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2022-09-15T02:14:34Z
dc.identifier.eissn
1573-7233
dc.journal.volume
39
dc.journal.number
3
dc.journal.pagination
933-952
dc.journal.pais
Países Bajos
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dc.description.fil
Fil: Lopez Bergami, Pablo Roberto. Universidad Maimónides. Área de Investigaciones Biomédicas y Biotecnológicas. Centro de Estudios Biomédicos, Biotecnológicos, Ambientales y de Diagnóstico. Departamento de Estudios Biomédicos y Biotecnológicos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
dc.description.fil
Fil: Barbero, Gastón Alexis. Universidad Maimónides. Área de Investigaciones Biomédicas y Biotecnológicas. Centro de Estudios Biomédicos, Biotecnológicos, Ambientales y de Diagnóstico. Departamento de Estudios Biomédicos y Biotecnológicos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
dc.journal.title
Cancer And Metastasis Reviews
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dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://link.springer.com/10.1007/s10555-020-09878-7
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1007/s10555-020-09878-7
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