CGI-99 Promotes Breast Cancer Metastasis Via Autocrine Interleukin-6 Signaling

Overview

Journal Oncogene

Specialties Molecular Biology
Oncology

Date 2017 Feb 7

PMID 28166202

Citations 19

Authors

C Lin

W Liao

Y Jian

Y Peng

X Zhang

L Ye

Y Cui

B Wang

X Wu

Z Xiong

S Wu

J Li

X Wang

L Song

Affiliations

Soon will be listed here.

Abstract

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-6-receptor 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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