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TRAIL ‐induced miR‐146a expression suppresses CXCR 4‐mediated human breast cancer migration
Author(s) -
Wang Dongsheng,
Liu Dan,
Gao Jing,
Liu Min,
Liu Shilian,
Jiang Minghong,
Liu Yanxin,
Zheng Dexian
Publication year - 2013
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.12323
Subject(s) - apoptosis , cancer research , breast cancer , metastasis , cancer , cancer cell , tumor necrosis factor alpha , autophagy , cell migration , medicine , biology , immunology , cell , biochemistry , genetics
Tumor necrosis factor‐related apoptosis‐inducing ligand ( TRAIL ) is considered a promising agent for cancer therapy, as this molecule induces apoptosis specifically in various cancer cells. Apart from apoptosis, TRAIL also induces non‐apoptotic signals, such as those for autophagy, proliferation and metastasis in cancer cells. In the present study, we report that TRAIL suppressed CXCR 4‐mediated human breast cancer MDA ‐ MB ‐231 cell migration by up‐regulating miR‐146a expression through NF ‐κB. TRAIL receptor 1 ( TRAIL ‐R1, DR 4) was highly expressed in TRAIL ‐treated MDA ‐ MB ‐231 cells. A neutralization antibody against DR 4 specifically blocked TRAIL ‐induced NF ‐κB activation and miR‐146a expression. These results were confirmed in a human breast cancer xenograft mouse model, suggesting that TRAIL significantly enhanced miR‐146a expression and suppressed CXCR 4 expression, indicating that TRAIL ‐induced miR‐146a up‐regulation is negatively associated with CXCR 4 expression. These findings suggest that TRAIL ‐induced miR‐146a expression suppresses CXCR 4‐mediated human breast cancer migration, and provide further insight into the non‐apoptotic function of TRAIL in the prevention of metastasis as a therapy for breast cancer.