摘要：SummaryActivity of liver x receptor (LXR), the homeostatic regulator of cholesterol metabolism, is elevated in triple-negative breast cancer (BCa) relative to other BCa subtypes, driving drug resistance and metastatic gene signatures. 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. Here, we report seven LXR splice variants, three of which have not previously been reported and five that were prognostic for disease-free survival. Expression of full-length LXRα splice variants was associated with poor prognosis, consistent with a role as an oncogenic driver of triple-negative tumor pathophysiology. Contrary to this was the observation that high expression of truncated LXRα splice variants or any LXRβ splice variant was associated with longer survival. These findings indicate that LXR isoform abundance is an important aspect of understanding the link between dysregulated cholesterol metabolism and cancer pathophysiology.Graphical abstractDisplay OmittedHighlights•LXR splicing is extensive in breast cancer•Three new LXR splice variants are confirmed at transcript and protein level•Full-length LXRα is associated with shorter disease-free survival in patients with TNBC•LXRβ or truncated LXRα variants associate with better prognosisMolecular biology; Molecular mechanism of gene regulation; Cancer systems biology; Cancer
