Dicer elicits paclitaxel chemosensitization and suppresses cancer stemness in breast cancer by repressing AXL

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

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)3916-3928
Number of pages13
JournalCancer Research
Volume76
Issue number13
DOIs
Publication statusPublished - Jul 1 2016

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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