Artikel ; Online: Splicing factor
2019 Band 20, Heft 2
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 ...
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. |
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Mesh-Begriff(e) | Alternative Splicing ; Antineoplastic Agents/pharmacology ; Breast Neoplasms/drug therapy ; Breast Neoplasms/genetics ; Breast Neoplasms/metabolism ; Breast Neoplasms/pathology ; Cell Line, Tumor ; Energy Metabolism ; Epithelial-Mesenchymal Transition/genetics ; Female ; Gene Expression Regulation, Neoplastic ; Gene Knockdown Techniques ; Humans ; Metabolic Networks and Pathways ; Proportional Hazards Models ; RNA Splicing Factors/metabolism ; RNA-Binding Proteins/genetics ; RNA-Binding Proteins/metabolism ; Receptors, Estrogen/metabolism |
Chemische Substanzen | Antineoplastic Agents ; ESRP1 protein, human ; RNA Splicing Factors ; RNA-Binding Proteins ; Receptors, Estrogen |
Sprache | Englisch |
Erscheinungsdatum | 2019-01-21 |
Erscheinungsland | England |
Dokumenttyp | Journal Article ; Research Support, Non-U.S. Gov't |
ZDB-ID | 2020896-0 |
ISSN | 1469-3178 ; 1469-221X |
ISSN (online) | 1469-3178 |
ISSN | 1469-221X |
DOI | 10.15252/embr.201846078 |
Datenquelle | MEDical Literature Analysis and Retrieval System OnLINE |
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