Splice-Variant Knock-Out of TGFβ Receptors Perturbates the Proteome of Ovarian Carcinoma Cells
Copyright policy )Splice-Variant Knock-Out of TGFβ Receptors Perturbates the Proteome of Ovarian Carcinoma Cells
The aim of this study was to analyze the biological role of different transforming growth factor-β (TGFβ) receptor splice variants in ovarian carcinoma (OC). Specific receptor variant knockouts (KO) were prepared using the CRISPR/Cas9 genome editing system in two OC cell lines, TβRI variant 1 (TβRIv1) KO in ES-2 cells and TβRII variant 1 (TβRIIv1) KO in OVCAR-8 cells. Control and KO cells were compared by proteomic analysis, functional tests, analysis of epithelial–mesenchymal transition (EMT) drivers, and Western blot of signaling proteins. Proteomic analysis revealed significant changes in protein pathways in the KO cells. TβRIv1 KO resulted in a significant reduction in both cellular motility and invasion, while TβRIIv1 KO significantly reduced cellular motility and increased Reactive Oxygen Species (ROS) production. Both receptor variant KOs reduced MET protein levels. Of the EMT drivers, a significant decrease in TWIST protein expression, and increase in SNAIL protein and MALAT1 mRNA levels were observed in the TβRIIv1 KO compared to control. A significant decrease in JNK1 and JNK2 activation was found in the TβRIv1 KO compared to control cells. These findings provide new insight regarding the biological role of the TGFβ receptor variants in the biology and potentially the progression of OC.
- Hebrew University of Jerusalem Israel
- Oslo University Hospital Norway
- Institute of Clinical Medicine, University of Oslo Norway
- University of Oslo Norway
- Department of Pathology Taiwan
Ovarian Neoplasms, Proteomics, Epithelial-Mesenchymal Transition, Twist-Related Protein 1, Receptor, Transforming Growth Factor-beta Type I, Receptor, Transforming Growth Factor-beta Type II, Nuclear Proteins, Proto-Oncogene Proteins c-met, transforming growth factor-β; TGFβ; receptor splice variants; ovarian carcinoma; proteomics; CRISPR/Cas9 KO’s, Article, Gene Expression Regulation, Neoplastic, Alternative Splicing, Gene Knockout Techniques, Cell Movement, Cell Line, Tumor, Humans, Female, RNA, Long Noncoding, Protein Interaction Maps, Snail Family Transcription Factors, Reactive Oxygen Species
Ovarian Neoplasms, Proteomics, Epithelial-Mesenchymal Transition, Twist-Related Protein 1, Receptor, Transforming Growth Factor-beta Type I, Receptor, Transforming Growth Factor-beta Type II, Nuclear Proteins, Proto-Oncogene Proteins c-met, transforming growth factor-β; TGFβ; receptor splice variants; ovarian carcinoma; proteomics; CRISPR/Cas9 KO’s, Article, Gene Expression Regulation, Neoplastic, Alternative Splicing, Gene Knockout Techniques, Cell Movement, Cell Line, Tumor, Humans, Female, RNA, Long Noncoding, Protein Interaction Maps, Snail Family Transcription Factors, Reactive Oxygen Species
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