HMGB1 Promotes Prostate Cancer Development and Metastasis by Interacting with Brahma-Related Gene 1 and Activating the Akt Signaling Pathway
: We have previously shown that high-mobility group box 1 ( ) is an independent biomarker for shortened survival of prostate cancer (PCa) patients. However, the specific role of in tumor development and progression remains largely unknown. In this study, we investigated the molecular mechanisms of i...
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Veröffentlicht in: | Theranostics 2019-01, Vol.9 (18), p.5166-5182 |
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Hauptverfasser: | , , , , , , , , |
Format: | Artikel |
Sprache: | eng |
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Zusammenfassung: | : We have previously shown that high-mobility group box 1 (
) is an independent biomarker for shortened survival of prostate cancer (PCa) patients. However, the specific role of
in tumor development and progression remains largely unknown. In this study, we investigated the molecular mechanisms of
in PCa tumorigenesis.
: Gain-of-function and loss-of-function experiments were used to determine the biological functions of
both
and
. Bioinformatic analysis, immunoprecipitation, and immunofluorescence assays were applied to discern and examine the relationship between
and its potential targets. Specimens from 64 patients with PCa were analyzed for the expression of
and its relationship with Brahma-related gene 1 (
) was examined by immunohistochemistry.
: The results demonstrated that ectopic expression of
facilitated growth and metastasis of PCa by enhancing
signaling pathway and promoting epithelial-mesenchymal transition (EMT), while silencing of
showed the opposite effects. Mechanistically,
exerted these functions through its interaction with
which may augment
function and activate the
signaling pathway thereby promoting EMT. Importantly, both
and
expression was markedly increased in human PCa tissues.
: Taken together, these findings indicate that upregulation of
promotes PCa development
activation of
and accelerates metastasis through regulating
-mediated EMT.
could be used as a novel potential target for the treatment of PCa. |
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ISSN: | 1838-7640 1838-7640 |
DOI: | 10.7150/thno.33972 |