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Updated: May 11, 2026
Retroviral Overexpression of CXCR4 on Murine B-1a Cells and Adoptive Transfer for Targeted B-1a Cell Migration to the Bone Marrow and IgM Production
Published on: May 31, 2020
TRAIL-induced miR-146a expression suppresses CXCR4-mediated human breast cancer migration
Dongsheng Wang1, Dan Liu, Jing Gao
1National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Abstract:
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 CXCR4-mediated human breast cancer MDA-MB-231 cell migration by up-regulating miR-146a expression through NF-κB. TRAIL receptor 1 (TRAIL-R1, DR4) was highly expressed in TRAIL-treated MDA-MB-231 cells. A neutralization antibody against DR4 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 CXCR4 expression, indicating that TRAIL-induced miR-146a up-regulation is negatively associated with CXCR4 expression. These findings suggest that TRAIL-induced miR-146a expression suppresses CXCR4-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.
Insights
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) suppresses breast cancer cell migration by increasing miR-146a. This pathway, involving NF-κB and TRAIL receptor 1, inhibits metastasis, offering new therapeutic strategies.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Therapeutics
Background:
- Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising cancer therapeutic agent due to its specific induction of apoptosis in cancer cells.
- Beyond apoptosis, TRAIL also modulates non-apoptotic signals, including autophagy, proliferation, and metastasis in cancer cells.
Purpose of the Study:
- To investigate the non-apoptotic effects of TRAIL on human breast cancer cell migration.
- To elucidate the molecular mechanisms underlying TRAIL's suppression of cancer cell migration, specifically focusing on the role of miR-146a and CXCR4.
Main Methods:
- Utilized human breast cancer MDA-MB-231 cell lines and a human breast cancer xenograft mouse model.
- Investigated the expression of miR-146a, CXCR4, and TRAIL receptor 1 (DR4) following TRAIL treatment.
- Employed a neutralization antibody against DR4 to assess its role in TRAIL-induced signaling pathways, including NF-κB activation.
Main Results:
- TRAIL suppressed CXCR4-mediated migration of MDA-MB-231 cells by up-regulating miR-146a expression via NF-κB activation.
- TRAIL treatment led to high expression of TRAIL receptor 1 (DR4) in MDA-MB-231 cells.
- Blocking DR4 with a neutralization antibody inhibited TRAIL-induced NF-κB activation and miR-146a expression.
- In vivo studies confirmed that TRAIL enhanced miR-146a expression and suppressed CXCR4 expression, demonstrating a negative association.
Conclusions:
- TRAIL-induced up-regulation of miR-146a effectively suppresses CXCR4-mediated human breast cancer cell migration.
- These findings highlight a novel non-apoptotic function of TRAIL in preventing cancer metastasis, suggesting its potential as a therapeutic strategy for breast cancer.
