Dicer Elicits Paclitaxel Chemosensitization and Suppresses Cancer Stemness in Breast Cancer by Repressing AXL
| Autor: | Yi Wen Chang, Ching Feng Chiu, Po Chun Tseng, Hsin An Chen, Ting Yu Chang, Weu Wang, Tsang Chih Kuo, Mien Chie Hung, Jen Liang Su |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
Ribonuclease III
0301 basic medicine Cancer Research medicine.medical_treatment Cell Mice SCID Bioinformatics DEAD-box RNA Helicases Mitogen-Activated Protein Kinase 14 Mice chemistry.chemical_compound 0302 clinical medicine Mice Inbred NOD Chemosensitization Tumor Cells Cultured biology medicine.anatomical_structure Oncology Paclitaxel 030220 oncology & carcinogenesis Neoplastic Stem Cells Female Adenovirus E1A Proteins Breast Neoplasms Adenoviridae 03 medical and health sciences Breast cancer Proto-Oncogene Proteins microRNA Biomarkers Tumor medicine Animals Humans MAPK14 Chemotherapy business.industry Receptor Protein-Tyrosine Kinases medicine.disease Antineoplastic Agents Phytogenic Xenograft Model Antitumor Assays Axl Receptor Tyrosine Kinase MicroRNAs 030104 developmental biology chemistry CCAAT-Enhancer-Binding Proteins biology.protein Cancer research business Dicer |
| Zdroj: | Cancer Research. 76:3916-3928 |
| ISSN: | 1538-7445 0008-5472 |
| DOI: | 10.1158/0008-5472.can-15-2555 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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