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dc.contributor.authorAtapattu, L
dc.contributor.authorSaha, N
dc.contributor.authorChheang, C
dc.contributor.authorEissman, MF
dc.contributor.authorXu, K
dc.contributor.authorVail, ME
dc.contributor.authorHii, L
dc.contributor.authorLlerena, C
dc.contributor.authorLiu, Z
dc.contributor.authorHorvay, K
dc.contributor.authorAbud, HE
dc.contributor.authorKusebauch, U
dc.contributor.authorMoritz, RL
dc.contributor.authorDing, B-S
dc.contributor.authorCao, Z
dc.contributor.authorRafii, S
dc.contributor.authorErnst, M
dc.contributor.authorScott, AM
dc.contributor.authorNikolov, DB
dc.contributor.authorLackmann, M
dc.contributor.authorJanes, PW
dc.date.accessioned2021-02-05T01:14:29Z
dc.date.available2021-02-05T01:14:29Z
dc.date.issued2016-08-22
dc.identifierpii: jem.20151095
dc.identifier.citationAtapattu, L., Saha, N., Chheang, C., Eissman, M. F., Xu, K., Vail, M. E., Hii, L., Llerena, C., Liu, Z., Horvay, K., Abud, H. E., Kusebauch, U., Moritz, R. L., Ding, B. -S., Cao, Z., Rafii, S., Ernst, M., Scott, A. M., Nikolov, D. B. ,... Janes, P. W. (2016). An activated form of ADAM10 is tumor selective and regulates cancer stem-like cells and tumor growth. JOURNAL OF EXPERIMENTAL MEDICINE, 213 (9), pp.1741-1757. https://doi.org/10.1084/jem.20151095.
dc.identifier.issn0022-1007
dc.identifier.urihttp://hdl.handle.net/11343/260322
dc.description.abstractThe transmembrane metalloprotease ADAM10 sheds a range of cell surface proteins, including ligands and receptors of the Notch, Eph, and erbB families, thereby activating signaling pathways critical for tumor initiation and maintenance. ADAM10 is thus a promising therapeutic target. Although widely expressed, its activity is normally tightly regulated. We now report prevalence of an active form of ADAM10 in tumors compared with normal tissues, in mouse models and humans, identified by our conformation-specific antibody mAb 8C7. Structure/function experiments indicate mAb 8C7 binds an active conformation dependent on disulfide isomerization and oxidative conditions, common in tumors. Moreover, this active ADAM10 form marks cancer stem-like cells with active Notch signaling, known to mediate chemoresistance. Importantly, specific targeting of active ADAM10 with 8C7 inhibits Notch activity and tumor growth in mouse models, particularly regrowth after chemotherapy. Our results indicate targeted inhibition of active ADAM10 as a potential therapy for ADAM10-dependent tumor development and drug resistance.
dc.languageEnglish
dc.publisherROCKEFELLER UNIV PRESS
dc.rights.urihttps://creativecommons.org/licenses/by-nc-sa/4.0
dc.titleAn activated form of ADAM10 is tumor selective and regulates cancer stem-like cells and tumor growth
dc.typeJournal Article
dc.identifier.doi10.1084/jem.20151095
melbourne.affiliation.departmentMedicine (Austin & Northern Health)
melbourne.affiliation.departmentSurgery (RMH)
melbourne.affiliation.facultyMedicine, Dentistry & Health Sciences
melbourne.source.titleJournal of Experimental Medicine
melbourne.source.volume213
melbourne.source.issue9
melbourne.source.pages1741-1757
dc.rights.licenseCC BY-NC-SA
melbourne.elementsid1101682
melbourne.contributor.authorErnst, Matthias
melbourne.contributor.authorLiu, Zhanqi
melbourne.contributor.authorScott, Andrew
dc.identifier.eissn1540-9538
melbourne.accessrightsOpen Access


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