dc.creator | Medina, María Victoria | |
dc.creator | D´Agostino, Agata | |
dc.creator | Ma, Qi | |
dc.creator | Eroles, Pilar | |
dc.creator | Cavallin, Lucas | |
dc.creator | Chiozzini, Chiara | |
dc.creator | Sapochnik, Daiana | |
dc.creator | Cymeryng, Cora Betriz | |
dc.creator | Hyjek, Elizabeth | |
dc.creator | Cesarman, Ethel | |
dc.creator | Naipauer, Julian | |
dc.creator | Mesri, Enrique Alfredo | |
dc.creator | Coso, Omar Adrian | |
dc.date.accessioned | 2021-07-12T12:33:54Z | |
dc.date.accessioned | 2022-10-15T09:26:01Z | |
dc.date.available | 2021-07-12T12:33:54Z | |
dc.date.available | 2022-10-15T09:26:01Z | |
dc.date.created | 2021-07-12T12:33:54Z | |
dc.date.issued | 2020-10 | |
dc.identifier | Medina, 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.identifier | 1553-7366 | |
dc.identifier | http://hdl.handle.net/11336/135831 | |
dc.identifier | 1553-7374 | |
dc.identifier | CONICET Digital | |
dc.identifier | CONICET | |
dc.identifier.uri | https://repositorioslatinoamericanos.uchile.cl/handle/2250/4370262 | |
dc.description.abstract | Kaposi'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.language | eng | |
dc.publisher | Public Library of Science | |
dc.relation | info:eu-repo/semantics/altIdentifier/url/https://pubmed.ncbi.nlm.nih.gov/33057440/ | |
dc.relation | info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1371/journal.ppat.1009006 | |
dc.rights | https://creativecommons.org/licenses/by-nc-sa/2.5/ar/ | |
dc.rights | info:eu-repo/semantics/openAccess | |
dc.subject | KHSV G-PROTEIN COUPLED RECEPTOR vGPCR | |
dc.subject | CYCLOOXIGENASE-2 | |
dc.subject | KAPOSI'S SARCOMA | |
dc.subject | ANGIOGENESIS | |
dc.title | KSHV G-protein coupled receptor vGPCR oncogenic signaling upregulation of Cyclooxygenase-2 expression mediates angiogenesis and tumorigenesis in Kaposi's sarcoma | |
dc.type | info:eu-repo/semantics/article | |
dc.type | info:ar-repo/semantics/artículo | |
dc.type | info:eu-repo/semantics/publishedVersion | |