BTF3 sustains cancer stem-like phenotype of prostate cancer via stabilization of BMI1

Abstract

Background Cancer stem-like traits contribute to prostate cancer (PCa) progression and metastasis. Deciphering the novel molecular mechanisms underlying stem-like traits may provide important insight for developing novel therapeutics. Methods Immunohistochemistry and immunofluorescence assays in prostatic tissues; gain- and loss-of-function analyses using ectopic overexpression and shRNAs in PCa cell lines; measurements of tumorigenic and stemness properties, and transcription in vitro and in vivo; transcriptional analysis in public databases. Results We identified that overexpression of BTF3 in PCa tissues and BTF3 expression highly correlates to stem-like traits. Cancer stem-like characteristics in PCa including self-renewal and metastatic potential were impaired by BTF3 loss and promoted by BTF3 overexpression. Mechanistically, BTF3 could stabilize BMI1, which is a crucial regulator of prostate stem cell self-renewal. More importantly, our data revealed that BTF3 is highly predictive of poor prognosis and may help in risk stratification of PCa patients. Conclusions BTF3 promotes PCa progression though modeling stem-like traits in PCa. BTF3 represents a stratification marker in PCa progression and outcomes. Electronic supplementary material The online version of this article (10.1186/s13046-019-1222-z) contains supplementary material, which is available to authorized users.

Genome-Wide DNA Methylation Profiles in Community Members Exposed to the World Trade Center Disaster

“…Among the rest of the top 15 differentially methylated probes, there were several other genes that may play a role in cancer development. BMI1 is a cancer stem cell marker [ 29 ] that has been implicated in acute myeloid leukemia [ 30 ], cervical cancer [ 31 ], and prostate cancer [ 32 ], among others, by acting as a chromatic remodeler of regulatory genes. EEF1A2 expression is elevated in poor prognosis of triple negative breast cancers [ 33 ].…”

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“…These data were confirmed from a preclinical study published by Bonnet et al in 1997 demonstrating that cells capable to generate human AML (Acute Myeloid Leukemia) in xenograft models had proliferative capacities and the ability to differentiate and self-renew indicating that normal stem cells, rather than committed progenitor cells, were the target for the neoplastic transformation [24]. Since then, the presence of CSC has been reported in several different type of tumors including breast [25], colorectal [26,27,28], prostatic [29], central nervous system cancers [30], melanomas [31] and sarcomas [32].…”

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