BMI-1 Promotes Ewing Sarcoma Tumorigenicity Independent of CDKN2A Repression

Division of Hematology-Oncology, Department of Pediatrics, Childrens Hospital Los Angeles, CA 90027, USA.
Cancer Research (Impact Factor: 9.33). 09/2008; 68(16):6507-15. DOI: 10.1158/0008-5472.CAN-07-6152
Source: PubMed

ABSTRACT Deregulation of the polycomb group gene BMI-1 is implicated in the pathogenesis of many human cancers. In this study, we have investigated if the Ewing sarcoma family of tumors (ESFT) expresses BMI-1 and whether it functions as an oncogene in this highly aggressive group of bone and soft tissue tumors. Our data show that BMI-1 is highly expressed by ESFT cells and that, although it does not significantly affect proliferation or survival, BMI-1 actively promotes anchorage-independent growth in vitro and tumorigenicity in vivo. Moreover, we find that BMI-1 promotes the tumorigenicity of both p16 wild-type and p16-null cell lines, demonstrating that the mechanism of BMI-1 oncogenic function in ESFT is, at least in part, independent of CDKN2A repression. Expression profiling studies of ESFT cells following BMI-1 knockdown reveal that BMI-1 regulates the expression of hundreds of downstream target genes including, in particular, genes involved in both differentiation and development as well as cell-cell and cell-matrix adhesion. Gain and loss of function assays confirm that BMI-1 represses the expression of the adhesion-associated basement membrane protein nidogen 1. In addition, although BMI-1 promotes ESFT adhesion, nidogen 1 inhibits cellular adhesion in vitro. Together, these data support a pivotal role for BMI-1 ESFT pathogenesis and suggest that its oncogenic function in these tumors is in part mediated through modulation of adhesion pathways.

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Available from: Elizabeth R Lawlor, Sep 29, 2015
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    • "Bmi-1 has been reported as an oncogene that controls cell proliferation and invasion (29). Furthermore, Bmi-1 is also involved in the self-renewal of cancer stem cells, which may result in tumor initiation (30,31). In the present study, Bmi-1 was found to be significantly overexpressed in the gastric cancer tissues and cell lines compared with the adjacent normal tissues and GES-1 normal gastric epithelial cells, respectively. "
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    Oncology letters 11/2014; 8(5):2345-2351. DOI:10.3892/ol.2014.2504 · 1.55 Impact Factor
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    • "Transcription factor Bmi-1(B lymphoma mouse moloney leukemia virus insertion region-1) is critical for the cell-cycle progression, and it can act as a positive regulator for DNA damage response and mitochondrial function [49]. It is also essential for promoting selfrenewal of several types of normal and cancer stem cells [50] [51] [52] [53]. "
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    ABSTRACT: MicroRNAs (miRNAs) are a class of endogenous, non-coding, 18-24 nucleotide length single-strand RNAs that could modulate gene expression at post-transcriptional level. Previous studies have shown that miR-128 enriched in the brain plays an important role in the development of nervous system and the maintenance of normal physical functions. Aberrant expression of miR-128 has been detected in many types of human tumors and its validated target genes are involved in cancer-related biological processes such as cell proliferation, differentiation and apoptosis. In this review, we will summarize the roles of miR-128 and its target genes in tumorigenesis and metastasis.
    Experimental Cell Research 08/2013; 319(20). DOI:10.1016/j.yexcr.2013.07.031 · 3.25 Impact Factor
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    • "fragment into pFB Hygro (adapted from pFB neo from Agilent, Cheshire, UK). Oligos targeting NDN (Supplementary Table 3) or a non-silencing control oligo (Douglas et al, 2008) were cloned into pRetroSuper-puro (Tomlinson et al, 2007). Constructs were transfected into PhoenixA (ATCC) using Mirus TransIT-293 (Cambridge Bioscience, Cambridge, UK). "
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