Theranostics 2019; 9(18):5166-5182. doi:10.7150/thno.33972
HMGB1 Promotes Prostate Cancer Development and Metastasis by Interacting with Brahma-Related Gene 1 and Activating the Akt Signaling Pathway
1. Department of Urology, Nanfang Hospital, Southern Medical University/ The First School of Clinical Medicine, Southern Medical University, Guangzhou 510515, China.
2. Department of Radiotherapy, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou 510095, China.
3. Department of Urology, Meizhou People's Hospital, No. 63, Huang Tang Road, Meizhou, 514031, Guangdong, People's Republic of China.
Lv D, Song X, Huang B, Yu YZ, Shu F, Wang C, Chen H, Zhang HB, Zhao S. HMGB1 Promotes Prostate Cancer Development and Metastasis by Interacting with Brahma-Related Gene 1 and Activating the Akt Signaling Pathway. Theranostics 2019; 9(18):5166-5182. doi:10.7150/thno.33972. Available from http://www.thno.org/v09p5166.htm
Background and Aim: We have previously shown that high-mobility group box 1 (HMGB1) is an independent biomarker for shortened survival of prostate cancer (PCa) patients. However, the specific role of HMGB1 in tumor development and progression remains largely unknown. In this study, we investigated the molecular mechanisms of HMGB1 in PCa tumorigenesis.
Methods: Gain-of-function and loss-of-function experiments were used to determine the biological functions of HMGB1 both in vitro and in vivo. Bioinformatic analysis, immunoprecipitation, and immunofluorescence assays were applied to discern and examine the relationship between HMGB1 and its potential targets. Specimens from 64 patients with PCa were analyzed for the expression of HMGB1 and its relationship with Brahma-related gene 1 (BRG1) was examined by immunohistochemistry.
Results: The results demonstrated that ectopic expression of HMGB1 facilitated growth and metastasis of PCa by enhancing Akt signaling pathway and promoting epithelial-mesenchymal transition (EMT), while silencing of HMGB1 showed the opposite effects. Mechanistically, HMGB1 exerted these functions through its interaction with BRG1 which may augment BRG1 function and activate the Akt signaling pathway thereby promoting EMT. Importantly, both HMGB1 and BRG1 expression was markedly increased in human PCa tissues.
Conclusions: Taken together, these findings indicate that upregulation of HMGB1 promotes PCa development via activation of Akt and accelerates metastasis through regulating BRG1-mediated EMT. HMGB1 could be used as a novel potential target for the treatment of PCa.
Keywords: HMGB1, epithelial-mesenchymal transition, Brahma-related gene 1, Akt pathway, prostate cancer