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Splicing factor <scp>ESRP</scp> 1 controls <scp>ER</scp> ‐positive breast cancer by altering metabolic pathways
- Source :
- EMBO reports. 20
- Publication Year :
- 2019
- Publisher :
- EMBO, 2019.
-
Abstract
- The epithelial splicing regulatory proteins 1 and 2 (ESRP1 and ESRP2) control the epithelial-to-mesenchymal transition (EMT) splicing program in cancer. However, their role in breast cancer recurrence is unclear. In this study, we report that high levels of ESRP1, but not ESRP2, are associated with poor prognosis in estrogen receptor positive (ER+) breast tumors. Knockdown of ESRP1 in endocrine-resistant breast cancer models decreases growth significantly and alters the EMT splicing signature, which we confirm using TCGA SpliceSeq data of ER+ BRCA tumors. However, these changes are not accompanied by the development of a mesenchymal phenotype or a change in key EMT-transcription factors. In tamoxifen-resistant cells, knockdown of ESRP1 affects lipid metabolism and oxidoreductase processes, resulting in the decreased expression of fatty acid synthase (FASN), stearoyl-CoA desaturase 1 (SCD1), and phosphoglycerate dehydrogenase (PHGDH) at both the mRNA and protein levels. Furthermore, ESRP1 knockdown increases the basal respiration and spare respiration capacity. This study reports a novel role for ESRP1 that could form the basis for the prevention of tamoxifen resistance in ER+ breast cancer.
- Subjects :
- 0303 health sciences
Gene knockdown
Alternative splicing
Cancer
Estrogen receptor
Biology
medicine.disease
Biochemistry
03 medical and health sciences
Splicing factor
0302 clinical medicine
Breast cancer
RNA splicing
Genetics
medicine
Cancer research
Phosphoglycerate dehydrogenase
skin and connective tissue diseases
Molecular Biology
030217 neurology & neurosurgery
030304 developmental biology
Subjects
Details
- ISSN :
- 14693178 and 1469221X
- Volume :
- 20
- Database :
- OpenAIRE
- Journal :
- EMBO reports
- Accession number :
- edsair.doi...........906e7fae122bde8923902e019e9d1fba