dc.creatorMedina, María Victoria
dc.creatorD´Agostino, Agata
dc.creatorMa, Qi
dc.creatorEroles, Pilar
dc.creatorCavallin, Lucas
dc.creatorChiozzini, Chiara
dc.creatorSapochnik, Daiana
dc.creatorCymeryng, Cora Betriz
dc.creatorHyjek, Elizabeth
dc.creatorCesarman, Ethel
dc.creatorNaipauer, Julian
dc.creatorMesri, Enrique Alfredo
dc.creatorCoso, Omar Adrian
dc.date.accessioned2021-07-12T12:33:54Z
dc.date.accessioned2022-10-15T09:26:01Z
dc.date.available2021-07-12T12:33:54Z
dc.date.available2022-10-15T09:26:01Z
dc.date.created2021-07-12T12:33:54Z
dc.date.issued2020-10
dc.identifierMedina, María Victoria; D´Agostino, Agata; Ma, Qi; Eroles, Pilar; Cavallin, Lucas; et al.; KSHV G-protein coupled receptor vGPCR oncogenic signaling upregulation of Cyclooxygenase-2 expression mediates angiogenesis and tumorigenesis in Kaposi's sarcoma; Public Library of Science; Plos Pathogens; 16; 10; 10-2020; 1-25
dc.identifier1553-7366
dc.identifierhttp://hdl.handle.net/11336/135831
dc.identifier1553-7374
dc.identifierCONICET Digital
dc.identifierCONICET
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/4370262
dc.description.abstractKaposi's sarcoma-associated herpesvirus (KSHV) vGPCR is a constitutively active G protein-coupled receptor that subverts proliferative and inflammatory signaling pathways to induce cell transformation in Kaposi's sarcoma. Cyclooxygenase-2 (COX-2) is an inflammatory mediator that plays a key regulatory role in the activation of tumor angiogenesis. Hereby we demonstrate, using two different transformed mouse models, and tumorigenic full KSHV genome-bearing cells, including KSHV-Bac16 based mutant system with a vGPCR deletion, that vGPCR upregulates COX-2 expression and activity, signaling through selective MAPK cascades. We show that vGPCR expression triggers signaling pathways that upregulate COX-2 levels due to a dual effect upon both its gene promoter region and, in mature mRNA, the 3'UTR region that control mRNA stability. Both events are mediated by signaling through ERK1/2 MAPK pathway. Inhibition of COX-2 in vGPCR-transformed cells impairs vGPCRdriven angiogenesis and treatment with the COX-2-selective inhibitory drug Celecoxib produces a significant decrease in tumor growth, pointing to COX-2 activity as critical for vGPCR oncogenicity in vivo and indicating that COX-2-mediated angiogenesis could play a role in KS tumorigenesis. These results, along with the overexpression of COX-2 in KS lesions, define COX-2 as a potential target for the prevention and treatment of KSHV-oncogenesis.
dc.languageeng
dc.publisherPublic Library of Science
dc.relationinfo:eu-repo/semantics/altIdentifier/url/https://pubmed.ncbi.nlm.nih.gov/33057440/
dc.relationinfo:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1371/journal.ppat.1009006
dc.rightshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectKHSV G-PROTEIN COUPLED RECEPTOR vGPCR
dc.subjectCYCLOOXIGENASE-2
dc.subjectKAPOSI'S SARCOMA
dc.subjectANGIOGENESIS
dc.titleKSHV G-protein coupled receptor vGPCR oncogenic signaling upregulation of Cyclooxygenase-2 expression mediates angiogenesis and tumorigenesis in Kaposi's sarcoma
dc.typeinfo:eu-repo/semantics/article
dc.typeinfo:ar-repo/semantics/artículo
dc.typeinfo:eu-repo/semantics/publishedVersion


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