NANOS1 restricts oral cancer cell motility and TGF-ß signaling

Julia Rosemann; Jonas Pyko; Roland Jacob; Jana Macho; Matthias Kappler; Alexander W Eckert; Monika Haemmerle; Tony Gutschner

doi:10.1016/j.ejcb.2024.151400

NANOS1 restricts oral cancer cell motility and TGF-ß signaling

Eur J Cell Biol. 2024 Feb 21;103(2):151400. doi: 10.1016/j.ejcb.2024.151400. Online ahead of print.

Authors

Julia Rosemann¹, Jonas Pyko¹, Roland Jacob¹, Jana Macho¹, Matthias Kappler², Alexander W Eckert³, Monika Haemmerle⁴, Tony Gutschner⁵

Affiliations

¹ Institute of Molecular Medicine, Section for RNA biology and pathogenesis, Martin Luther University Halle-Wittenberg, Halle 06120, Germany.
² Department of Oral and Maxillofacial Plastic Surgery, Martin Luther University Halle-Wittenberg, Halle 06120, Germany.
³ Department of Cranio Maxillofacial Surgery, Paracelsus Medical University, Nuremberg 90471, Germany.
⁴ Institute of Pathology, Section for Experimental Pathology, Martin Luther University Halle-Wittenberg, Halle 06120, Germany.
⁵ Institute of Molecular Medicine, Section for RNA biology and pathogenesis, Martin Luther University Halle-Wittenberg, Halle 06120, Germany. Electronic address: tony.gutschner@uk-halle.de.

PMID: 38401491
DOI: 10.1016/j.ejcb.2024.151400

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: EMT; HNSCC; Metastasis; OSCC; RBP; RNA-binding protein.