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HMGB1 Promotes Prostate Cancer Development and Metastasis by Interacting with Brahma-Related Gene 1 and Activating the Akt Signaling Pathway
- Source :
- Theranostics
- Publication Year :
- 2019
- Publisher :
- Ivyspring International Publisher, 2019.
-
Abstract
- 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.
- Subjects :
- Male
0301 basic medicine
Epithelial-Mesenchymal Transition
Carcinogenesis
Brahma-related gene 1
Mice, Nude
Medicine (miscellaneous)
Cell Cycle Proteins
chemical and pharmacologic phenomena
Biology
medicine.disease_cause
Metastasis
Phosphatidylinositol 3-Kinases
03 medical and health sciences
0302 clinical medicine
Cell Movement
Cell Line, Tumor
medicine
Animals
Humans
Gene silencing
Neoplasm Invasiveness
Epithelial–mesenchymal transition
HMGB1 Protein
Neoplasm Metastasis
Pharmacology, Toxicology and Pharmaceutics (miscellaneous)
Protein kinase B
PI3K/AKT/mTOR pathway
Aged
Cell Proliferation
HMGB1
Mice, Inbred BALB C
Akt/PKB signaling pathway
DNA Helicases
Nuclear Proteins
Prostatic Neoplasms
prostate cancer
medicine.disease
030104 developmental biology
030220 oncology & carcinogenesis
Cancer research
Ectopic expression
Proto-Oncogene Proteins c-akt
Akt pathway
Research Paper
Signal Transduction
Transcription Factors
Subjects
Details
- ISSN :
- 18387640
- Volume :
- 9
- Database :
- OpenAIRE
- Journal :
- Theranostics
- Accession number :
- edsair.doi.dedup.....2f95d357f27fc17e48f2843e4c4007c5