journal contribution
posted on 2023-03-30, 23:40 authored by Ting-Yu Chang, Hsin-An Chen, Ching-Feng Chiu, Yi-Wen Chang, Tsang-Chih Kuo, Po-Chun Tseng, Weu Wang, Mien-Chie Hung, Jen-Liang Su Description of additional methods and procedures used in the study. Also includes Supplementary Reference.
Funding
Ministry of Science and Technology (National Science Council) grants from Taiwan
National Health Research Institutes grant from Taiwan
Taipei Medical University-Shuang Ho Hospital, Ministry of Health and Welfare grant from Taiwan
History
ARTICLE 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.
