Research & Innovation
Publications
NANOS1 restricts oral cancer cell motility and TGF-ß signaling
PMU Author
Alexander W Eckert
All Authors
Julia Rosemann, Jonas Pyko, Roland Jacob, Jana Macho, Matthias Kappler, Alexander W Eckert, Monika Haemmerle, Tony Gutschner
Journal association
EUROPEAN JOURNAL OF CELL BIOLOGY
Abstract
Oral squamous cell carcinoma (OSCC) is the most frequent type of cancer of the head and neck area accounting for approx. 377,000 new cancer cases every year. The epithelial-to-mesenchymal transition (EMT) program plays an important role in OSCC progression and metastasis therefore contributing to a poor prognosis in patients with advanced disease. Transforming growth factor beta (TGF-ß) is a powerful inducer of EMT thereby increasing cancer cell aggressiveness. Here, we aimed at identifying RNA-binding proteins (RBPs) that affect TGF-ß-induced EMT. To this end we treated oral cancer cells with TGF-ß and identified a total of 643 significantly deregulated protein-coding genes in response to TGF-ß. Of note, 19 genes encoded RBPs with NANOS1 being the most downregulated RBP. Subsequent cellular studies demonstrated a strong inhibitory effect of NANOS1 on migration and invasion of SAS oral cancer cells. Further mechanistic studies revealed an interaction of NANOS1 with the TGF-ß receptor 1 (TGFBR1) mRNA, leading to increased decay of this transcript and a reduced TGFBR1 protein expression, thereby preventing downstream TGF-ß/SMAD signaling. In summary, we identified NANOS1 as negative regulator of TGF-ß signaling in oral cancer cells.
Keywords
Humans, Signal Transduction, EPITHELIAL-MESENCHYMAL TRANSITION, Cell Line, Tumor, Mouth Neoplasms/metabolism, RNA-Binding Proteins/metabolism, Cell Movement, Transforming Growth Factor beta/metabolism, Receptor, Transforming Growth Factor-beta Type I/metabolism, Carcinoma, Squamous Cell/metabolism, Gene Expression Regulation, Neoplastic