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Sci Rep. 2016 Jan 18;6:19435. doi: 10.1038/srep19435.

Squalene epoxidase is a bona fide oncogene by amplification with clinical relevance in breast cancer.

Author information

1
J.-C. Heuson Breast Cancer Translational Research Laboratory, Institut Jules Bordet, Brussels BE.
2
Department of Internal Medicine (Di.M.I.), University of Genova, Genova IT.
3
Unità di Patologia Oncologica CeSI, Università "G. D'Annunzio", Chieti Scalo (Chieti) IT.
4
Istituto di Ricovero e Cura a Carattere Scientifico Azienda Ospedaliera-Universitaria San Martino and National Cancer Institute, Genova IT.

Abstract

SQLE encodes squalene epoxidase, a key enzyme in cholesterol synthesis. SQLE has sporadically been reported among copy-number driven transcripts in multi-omics cancer projects. Yet, its functional relevance has never been subjected to systematic analyses. Here, we assessed the correlation of SQLE copy number (CN) and gene expression (GE) across multiple cancer types, focusing on the clinico-pathological associations in breast cancer (BC). We then investigated whether any biological effect of SQLE inhibition could be observed in BC cell line models. Breast, ovarian, and colorectal cancers showed the highest CN driven GE among 8,783 cases from 22 cancer types, with BC presenting the strongest one. SQLE overexpression was more prevalent in aggressive BC, and was an independent prognostic factor of unfavorable outcome. Through SQLE pharmacological inhibition and silencing in a panel of BC cell lines portraying the diversity of SQLE CN and GE, we demonstrated that SQLE inhibition resulted in a copy-dosage correlated decrease in cell viability, and in a noticeable increase in replication time, only in lines with detectable SQLE transcript. Altogether, our results pinpoint SQLE as a bona fide metabolic oncogene by amplification, and as a therapeutic target in BC. These findings could have implications in other cancer types.

PMID:
26777065
PMCID:
PMC4726025
DOI:
10.1038/srep19435
[Indexed for MEDLINE]
Free PMC Article

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