| Title: |
Pharmacological inhibition of frizzled 4 delays cell cycle progression and limits oral squamous cell carcinoma growth |
| Authors: |
Destefani, Riccardo; Valookkaran, Ilaria J.; Bensland, Sabrina; Meisel, Christian T.; Porcheri, Cristina |
| Contributors: |
Olga Mayenfisch Stiftung; Julius Müller Stiftung; Krebsliga Schweiz; Julius Klaus-Stiftung für Genetik und Sozialanthropologie |
| Source: |
Frontiers in Cell and Developmental Biology ; volume 14 ; ISSN 2296-634X |
| Publisher Information: |
Frontiers Media SA |
| Publication Year: |
2026 |
| Collection: |
Frontiers (Publisher - via CrossRef) |
| Description: |
Oral squamous cell carcinoma is an aggressive malignancy driven by aberrant signaling pathways, with Wnt signaling acting as a central regulator of proliferation, tumor-microenvironment interactions, and oncogenic growth. Here, we focus on Frizzled-4, a Wnt receptor with context-dependent functions in epithelial cancers. We show that pharmacological inhibition of Frizzled-4 delays cell cycle progression, and reduces proliferative capacity. These effects are accompanied by suppressed metabolism of retinoic acid, suggesting that Frizzled-4 inhibition stabilizes intracellular retinoic acid levels, which ultimately contributes to the observed cell cycle slowdown. Blocking retinoic acid signaling reverses the cell cycle effects of Frizzled-4 inhibition, confirming that retinoic acid-dependent regulation operates downstream of Frizzled-4. By restraining uncontrolled proliferation and attenuating oncogenic signaling, Frizzled-4 emerges as a key molecular node in oral squamous cell carcinoma, highlighting its potential as a therapeutic target to counteract Wnt-driven tumor growth. |
| Document Type: |
article in journal/newspaper |
| Language: |
unknown |
| DOI: |
10.3389/fcell.2026.1756565 |
| DOI: |
10.3389/fcell.2026.1756565/full |
| Availability: |
https://doi.org/10.3389/fcell.2026.1756565; https://www.frontiersin.org/articles/10.3389/fcell.2026.1756565/full |
| Rights: |
https://creativecommons.org/licenses/by/4.0/ |
| Accession Number: |
edsbas.995DA5EF |
| Database: |
BASE |