An Autocrine Wnt5a Loop Promotes NF-κB Pathway Activation and Cytokine/Chemokine Secretion in Melanoma

Autor:	Sharon DeMorrow, María Victoria Castro, Gastón Barbero, Natalia Brenda Fernández, María Belén Villanueva, María Josefina Quezada, Pablo Lopez-Bergami
Rok vydání:	2019
Předmět:	0301 basic medicine Chemokine medicine.medical_treatment Dishevelled Proteins IκB kinase Receptor Tyrosine Kinase-like Orphan Receptors Wnt-5a Protein Article NF-κB 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Cell Line Tumor medicine melanoma cytokine Humans Phosphorylation Autocrine signalling lcsh:QH301-705.5 Protein kinase B biology RELB Akt chemokine NF-kappa B Transcription Factor RelA General Medicine Wnt5a TNF Receptor-Associated Factor 2 I-kappa B Kinase body regions Autocrine Communication 030104 developmental biology Cytokine lcsh:Biology (General) chemistry 030220 oncology & carcinogenesis Chemokine secretion embryonic structures biology.protein Cancer research Cytokines I-kappa B Proteins sense organs Chemokines Proto-Oncogene Proteins c-akt Signal Transduction
Zdroj:	Cells Volume 8 Issue 9 Cells, Vol 8, Iss 9, p 1060 (2019)
ISSN:	2073-4409
Popis:	Wnt5a signaling has been implicated in the progression of cancer by regulating multiple cellular processes, largely migration and invasion, epithelial-mesenchymal transition (EMT), and metastasis. Since Wnt5a signaling has also been involved in inflammatory processes in infectious and inflammatory diseases, we addressed the role of Wnt5a in regulating NF-&kappa B, a pivotal mediator of inflammatory responses, in the context of cancer. The treatment of melanoma cells with Wnt5a induced phosphorylation of the NF-&kappa B subunit p65 as well as IKK phosphorylation and I&kappa B degradation. By using cDNA overexpression, RNA interference, and dominant negative mutants we determined that ROR1, Dvl2, and Akt (from the Wnt5a pathway) and TRAF2 and RIP (from the NF-&kappa B pathway) are required for the Wnt5a/NF-&kappa B crosstalk. Wnt5a also induced p65 nuclear translocation and increased NF-&kappa B activity as evidenced by reporter assays and a NF-&kappa B-specific upregulation of RelB, Bcl-2, and Cyclin D1. Further, stimulation of melanoma cells with Wnt5a increased the secretion of cytokines and chemokines, including IL-6, IL-8, IL-11, and IL-6 soluble receptor, MCP-1, and TNF soluble receptor I. The inhibition of endogenous Wnt5a demonstrated that an autocrine Wnt5a loop is a major regulator of the NF-&kappa B pathway in melanoma. Taken together, these results indicate that Wnt5a activates the NF-&kappa B pathway and has an immunomodulatory effect on melanoma through the secretion of cytokines and chemokines.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c91322460e5f7a7d18f95a267f7076df https://pubmed.ncbi.nlm.nih.gov/31510045 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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