期刊
ONCOGENE
卷 36, 期 26, 页码 3695-3705出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/onc.2016.525
关键词
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资金
- Ministry of Science and Technology of China [973-2014CB910604]
- Natural Science Foundation of China [81472546, 81672854, 81530082, 81272198, 81572687, 81325013, 91529301, 81572688]
- Science and Technology of Guangdong Province [2016A030308002, 2014A030313008, 2014A030313220]
- Science and Technology Program of Guangzhou [15020077]
- Guangdong Esophageal Cancer Institute [M201409]
Metastatic relapse remains largely incurable and a major challenge of clinical management in breast cancer, but the underlying mechanisms are poorly understood. Herein, we report that CGI-99 is overexpressed in breast cancer tissues from patients with metastatic recurrence within 5 years. High CGI-99 significantly predicts poorer 5-year metastasis-free patient survival. We find that CGI-99 increases breast cancer stem cell properties, and potentiates efficient tumor lung colonization and outgrowth in vivo. Furthermore, we demonstrate that CGI-99 activates the autocrine interleukin-6 (IL-6)/STAT3 signaling by increasing the accumulation and activity of RNA polymerase II and p300 cofactor at the proximal promoter of IL-6. Importantly, delivery of the IL-6receptor humanized monoclonal antibody tocilizumab robustly abrogates CGI-99-induced metastasis in vivo. Finally, we find that high levels of CGI-99 are significantly correlated with STAT3 hyperactivation in breast cancer patients. These findings reveal a potential mechanism for constitutive activation of autocrine IL-6/STAT3 signaling and may suggest a novel target for clinical intervention in breast cancer.
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