IL13R alpha 2-and EGFR-targeted pseudomonas exotoxin potentiates the TRAIL-mediated death of GBM cells

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dc.authorid0000-0002-9096-1512
dc.contributor.authorKarakaş, Nihal
dc.contributor.authorStuckey, Daniel
dc.contributor.authorRevai-Lechtich, Esther
dc.contributor.authorShah, Khalid
dc.date.accessioned2021-06-17T07:34:55Z
dc.date.available2021-06-17T07:34:55Z
dc.date.issued2021
dc.departmentİstanbul Medipol Üniversitesi, Tıp Fakültesi, Temel Tıp Bilimleri Bölümü, Tıbbi Biyoloji Ana Bilim Dalı
dc.description.abstractGlioblastomas (GBMs) are refractory to current treatments and novel therapeutic approaches need to be explored. Pro-apoptotic tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is tumor-specific and has been shown to induce apoptosis and subsequently kill GBM cells. However, approximately 50% of GBM cells are resistant to TRAIL and a combination of TRAIL with other therapeutics is necessary to induce mechanism-based cell death in TRAIL-resistant GBMs. The present study examined the ability of the tumor cell surface receptor, interleukin (IL)-13 receptor alpha 2 (IL13R alpha 2)- and epidermal growth factor receptor (EGFR)-targeted pseudomonas exotoxin (PE) to sensitize TRAIL-resistant GBM cells and assessed the dual effects of interleukin 13-PE (IL13-PE) or EGFR nanobody-PE (ENb-PE) and TRAIL for the treatment of a broad range of brain tumors with a distinct TRAIL therapeutic response. Receptor targeted toxins upregulated TRAIL death receptors (DR4 and DR5) and suppressed the expression of anti-apoptotic FLICE-inhibitory protein (FLIP) and X-linked inhibitor of apoptosis protein (XIAP). This also led to the induction of the cleavage of caspase-8 and caspase-9 and resulted in the sensitization of highly resistant established GBM and patient-derived GBM stem cell (GSC) lines to TRAIL-mediated apoptosis. These findings provide a mechanism-based strategy that may provide options for the cell-mediated delivery of bi-functional therapeutics to target a wide spectrum of TRAIL-resistant GBMs.
dc.identifier.citationKarakaş, N., Stuckey, D., Revai-Lechtich, E. ve Shah, K. (2021). IL13R alpha 2-and EGFR-targeted pseudomonas exotoxin potentiates the TRAIL-mediated death of GBM cells. International Journal of Molecular Medicine, 48(1). https://dx.doi.org/10.3892/ijmm.2021.4978
dc.identifier.doi10.3892/ijmm.2021.4978
dc.identifier.issn1107-3756
dc.identifier.issn1791-244X
dc.identifier.issue1
dc.identifier.scopusqualityQ1
dc.identifier.urihttps://dx.doi.org/10.3892/ijmm.2021.4978
dc.identifier.urihttps://hdl.handle.net/20.500.12511/7208
dc.identifier.volume48
dc.identifier.wosqualityQ2
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherSpandidos Publications Ltd
dc.relation.ispartofInternational Journal of Molecular Medicineen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.relation.tubitakinfo:eu-repo/grantAgreement/TUBITAK/SOBAG/RO1 CA138922
dc.relation.tubitakinfo:eu-repo/grantAgreement/TUBITAK/SOBAG/R01 CA201148
dc.rightsinfo:eu-repo/semantics/embargoedAccess
dc.subjectTumor Necrosis Factor-Related Apoptosis-Inducing Ligand
dc.subjectInterleukin-13 Receptor
dc.subjectPseudomonas Exotoxin
dc.subjectGlioblastoma
dc.subjectTargeted Therapy
dc.titleIL13R alpha 2-and EGFR-targeted pseudomonas exotoxin potentiates the TRAIL-mediated death of GBM cells
dc.typeArticle

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