Splice‐variant knock‐out of tgfβ receptors perturbates the proteome of ovarian carcinoma cells

Liora Jacobs Catane, Ofra Moshel, Yoav Smith, Ben Davidson, Reuven Reich*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

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 knock-outs (KO) were prepared using the CRISPR/Cas9 genome editing system in two OC cell lines, TβRI variant 1 (TβRІv1) KO in ES‐2 cells and TβRII variant 1 (TβRІIv1) 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 TβRІIv1 KO compared to control. A significant decrease in JNK1 and JNK2 activation was found in the TβRІv1 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.

Original languageEnglish
Article number12647
JournalInternational Journal of Molecular Sciences
Volume22
Issue number23
DOIs
StatePublished - 1 Dec 2021

Bibliographical note

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

  • CRISPR/Cas9 KO’s
  • Ovarian carcinoma
  • Proteomics
  • Receptor splice variants
  • TGFβ
  • Transforming growth factor‐β

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