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• W3167656306 abstract "Abstract The liver x receptors (LXR) alpha and beta are ligand-responsive transcription factors that link homeostatic control of lipid metabolism with cancer pathophysiology and prognosis. LXR activity is elevated in triple negative breast cancer relative to other breast cancer subtypes, driving gene signatures associated with drug resistance and metastasis. The loci encoding LXRα and LXRβ produce multiple alternatively spliced proteins, but the true range of variants and their relevance to cancer remain poorly defined. Seven splice variants of LXRα or LXRβ were detected. Three have not been recorded previously and five were prognostic. High expression of full length LXRα was associated with shorter disease-free survival but splice variants harbouring truncations of the ligand binding domain were prognostic for improved survival. All LXRβ variants were associated with longer disease-free survival. Mechanistically, while full length LXRα positively correlated with target gene expression in primary samples, LXRβ was inversely correlated. We conclude that canonical LXRα function is an oncogenic driver of triple negative tumour pathophysiology that can be countered by high expression of truncated splice variants and/or full length LXRβ. Highlights Expression of full length LXRα is associated with shorter disease-free survival of triple negative breast cancer patients A systematic evaluation of cell lines and primary tumour samples indicates LXR splicing is extensive in breast cancer Confirmation of three new LXR splice variants at transcript and protein level Expression of full length LXRβ or LXRα splice variants that harbour truncated ligand binding domains are associated with better prognosis Expression of LXR target genes is positively correlated with LXRα in relapsed patients and inversely correlated with LXRβ in survivors." @default.
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• W3167656306 date "2021-06-10" @default.
• W3167656306 modified "2023-09-24" @default.
• W3167656306 title "Comprehensive profiling of liver x receptor splicing in triple negative breast cancer reveals existence of novel splice variants that are prognostic for survival" @default.
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• W3167656306 doi "https://doi.org/10.1101/2021.06.09.445161" @default.
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