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dc.contributor.authorFlem-Karlsen, Karine
dc.contributor.authorTekle, Christina
dc.contributor.authorØyjord, Tove Ragnhild
dc.contributor.authorFlørenes, Vivi Ann
dc.contributor.authorMælandsmo, Gunhild Mari
dc.contributor.authorFodstad, Øystein
dc.contributor.authorNunes-Xavier, Caroline Elisabeth
dc.date.accessioned2019-10-11T12:47:15Z
dc.date.available2019-10-11T12:47:15Z
dc.date.issued2019-04-09
dc.description.abstractImmunoregulatory protein B7-H3 is involved in the oncogenic and metastatic potential of cancer cells, as well as in drug resistance. Resistance to conventional chemotherapy is an important aspect of melanoma treatment, and a better understanding of how B7-H3 enhances drug resistance may lead to the development of more effective therapies. We investigated the <i>in vitro</i> and <i>in vivo</i> sensitivity of chemotherapeutic agents dacarbazine (DTIC) and cisplatin in sensitive and drug resistant melanoma cells with knockdown expression of B7-H3. We found that knockdown of B7-H3 increased <i>in vitro</i> and <i>in vivo</i> sensitivity of melanoma cells to the chemotherapeutic agents dacarbazine (DTIC) and cisplatin, in parallel with a decrease in p38 MAPK phosphorylation. Importantly, in B7-H3 knockdown cells we observed an increase in the expression of dual-specific MAP kinase phosphatase (MKP) DUSP10, a MKP known to dephosphorylate and inactivate p38 MAPK. DUSP10 knockdown by siRNA resulted in a reversion of the increased DTIC-sensitivity seen in B7-H3 knockdown cells. Our findings highlight the potential therapeutic benefit of combining chemotherapy with B7-H3 inhibition, and indicate that B7-H3 mediated chemoresistance in melanoma cells is driven through a mechanism involving DUSP10-mediated inactivation of p38 MAPK.en_US
dc.descriptionSource at <a href=https://doi.org/10.1038/s41598-019-42303-w>https://doi.org/10.1038/s41598-019-42303-w</a>.en_US
dc.identifier.citationFlem-Karlsen, K., Tekle, C., Øyjord, T., Flørenes, V.A., Mælandsmo, G.M., Fodstad, Ø. & Nunes-Xavier, C.E. (2019). p38 MAPK activation through B7-H3-mediated DUSP10 repression promotes chemoresistance. <i>Scientific Reports, 9</i>, 5839. https://doi.org/10.1038/s41598-019-42303-wen_US
dc.identifier.cristinIDFRIDAID 1695256
dc.identifier.doi10.1038/s41598-019-42303-w
dc.identifier.issn2045-2322
dc.identifier.urihttps://hdl.handle.net/10037/16381
dc.language.isoengen_US
dc.publisherSpringer Natureen_US
dc.relation.journalScientific Reports
dc.relation.projectIDinfo:eu-repo/grantAgreement/RCN/FRIMEDBIO/239813/Norway/B7-H3/PTEN: a new axis for novel anti-cancer therapies in prostate cancer//en_US
dc.rights.accessRightsopenAccessen_US
dc.subjectVDP::Medical disciplines: 700::Clinical medical disciplines: 750::Oncology: 762en_US
dc.subjectVDP::Medisinske Fag: 700::Klinisk medisinske fag: 750::Onkologi: 762en_US
dc.subjectCancer therapeutic resistanceen_US
dc.subjectChemotherapyen_US
dc.titlep38 MAPK activation through B7-H3-mediated DUSP10 repression promotes chemoresistanceen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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