Abstract：
:Paclitaxel is a standard-of-care chemotherapy for breast cancer, despite the increasing recognition of its poor effectiveness in the treatment of patients with advanced disease. Here, we report that adenovirus-type 5 E1A-mediated elevation of the miRNA-processing enzyme Dicer is sufficient to enhance paclitaxel sensitization and reduce cancer stem-like cell properties in this setting. Elevating Dicer expression increased levels of the AXL kinase targeting miRNA miR-494, thereby repressing AXL expression to increase paclitaxel sensitivity. We found that Dicer expression was regulated at the transcription level by E1A, through activation of an MAPK14/CEBPα pathway. Our findings define a mechanism of E1A-mediated chemosensitization for paclitaxel, which is based upon the suppression of breast cancer stem-like cells, with potential implications for the diagnosis and treatment of breast cancer patients. Cancer Res; 76(13); 3916-28. ©2016 AACR.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Chang TY,Chen HA,Chiu CF,Chang YW,Kuo TC,Tseng PC,Wang W,Hung MC,Su JLdoi
10.1158/0008-5472.CAN-15-2555subject
Has Abstractpub_date
2016-07-01 00:00:00pages
3916-28issue
13eissn
0008-5472issn
1538-7445pii
0008-5472.CAN-15-2555journal_volume
76pub_type
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