Heparin-binding growth factor (HDGF) drives radioresistance in breast cancer by activating the STAT3 signaling pathway

Journal of Translational Medicine

Liheng Zhou¹  Guansheng Zhong²  Lei Zhang³  Xiaohua Chen⁴  Jianming Tang⁵  Lingyun Qiu⁶  Haibo Zhang⁶  Yan Ma⁷ 

[1] Department of Breast Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 200127, Shanghai, People’s Republic of China;Department of Breast Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, 310003, Hangzhou, People’s Republic of China;Department of Radiation Oncology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 200127, Shanghai, People’s Republic of China;Department of Radiation Oncology, The First Hospital of Lanzhou University, Lanzhou University, 730000, Lanzhou, Gansu, People’s Republic of China;Key Laboratory of Biotherapy and Regenerative Medicine of Gansu Province, The First Hospital of Lanzhou University, Lanzhou University, 730000, Lanzhou, Gansu, People’s Republic of China;Oncology Center, Department of Radiation Oncology, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, 310014, Hangzhou, Zhejiang, People’s Republic of China;The First School of Clinical Medicine, Lanzhou University, 730000, Lanzhou, People’s Republic of China;

关键词: HDGF;    STAT3 signaling pathway;    Radioresistance;    Breast cancer;   

DOI  :  10.1186/s12967-021-03021-y

来源: Springer

【 摘 要 】

Although reports implicate radioresistance as an important obstacle for the management of breast cancer, its molecular mechanism is elusive. Herein, we found that high HDGF levels are expressed significantly in breast cancer and exhibit a positive association with poor survival prognosis. Heparin-binding growth factor (HDGF) was upregulated in radioresistant breast cancer cells, however, its knockdown could reduce breast cancer radioresistant both in vitro and in vivo. Additionally, the binding of RXRα to HDGF promoter blocked HDGF transcriptional activity, consequently inhibiting breast cancer radioresistance. The enhanced radioresistant activity of HDGF is induced by TKT and STAT3, impacting the STAT3-Tyr705 and STAT3-Ser727 phosphorylation and STAT3 transcriptional activity. Notably, HDGF depletion renders radioresistant hypersensitive to the drug that targets STAT3 phosphorylation. This article demonstrates the novel function of HDGF as a promising molecular target for predicting radioresistance in breast cancer.

【 授权许可】

CC BY