AXL is crucial for E1A-enhanced therapeutic efficiency of EGFR tyrosine kinase inhibitors through NFI in breast cancer

AXL 对 E1A 通过 NFI 增强 EGFR 酪氨酸激酶抑制剂对乳腺癌的治疗效果至关重要

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作者:Chih-Ming Su, Tung-Wei Hsu, Shian-Ying Sung, Ming-Te Huang, Kuan-Chou Chen, Chih-Yang Huang, Chien Yi Chiang, Yen-Hao Su, Hsin-An Chen, Po-Hsiang Liao

Abstract

AXL which is a chemosensitizer protein for breast cancer cells in response to epidermal growth factor receptor-tyrosine kinase inhibitor and suppresses tumor growth. The clinical information show nuclear factor I (NFI)-C and NFI-X expression correlate with AXL expression in breast cancer patients. Following, we establish serial deletions of AXL promoter to identify regions required for Adenovirus-5 early region 1A (E1A)-mediated AXL suppression. All of the NFI family members were extensively studied for their expression and functions in regulating AXL. Moreover, E1A post-transcriptionally downregulates AXL expression through NFI. NFI-C and NFI-X, not NFI-A and NFI-B, resulting in cell death in response to EGFR-TKI. Our finding suggests that NFI-C and NFI-X are crucial regulators for AXL and significantly correlated with poor survival of breast cancer patients.

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