In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 72, No. 8_Supplement ( 2012-04-15), p. LB-31-LB-31
Abstract:
In advanced cancer including glioblastoma, the TGF-β pathway acts as an oncogenic factor and is considered a therapeutic target. Using a functional RNA-interference screen, we have identified the deubiquitinating enzyme USP15 as a critical component of the TGF-β signaling pathway. USP15 binds to the SMAD7-SMURF2 complex and deubiquitinates and stabilizes the TGF-β receptor I leading to an enhanced TGF-β signal. Importantly, we find that the USP15 gene is found amplified in glioblastoma, breast and ovarian cancer and that USP15 gene amplification confers poor prognosis in glioblastoma patients. Furthermore we demonstrate that downregulation or inhibition of USP15 in a patient-derived orthotopic mouse model of glioblastoma decreases TGF-β activity. Moreover, depletion of USP15 decreases the oncogenic capacity of patient-derived glioma-initiating cells due to the repression of TGF-β signaling. Our results show that USP15 regulates the TGF-β pathway and is a critical factor in glioblastoma pathogenesis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-31. doi:1538-7445.AM2012-LB-31
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2012-LB-31
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2012
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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