OXTR(High) stroma fibroblasts control the invasion pattern of oral squamous cell carcinoma via ERK5 signaling
Publication Year 2022-08-31,Volume 13,Issue #1,Page 5124
Journal Title
Nature Communications
The Pattern Of Invasion (POI) of tumor cells into adjacent normal tissues clinically predicts postoperative tumor metastasis/recurrence of early oral squamous cell carcinoma (OSCC), but the mechanisms underlying the development of these subtypes remain unclear. Focusing on the highest score of POIs (Worst POI, WPOI) present within each tumor, we observe a disease progression-driven shift of WPOI towards the high-risk type 4/5, associated with a mesenchymal phenotype in advanced OSCC. WPOI 4-5-derived cancer-associated fibroblasts (CAFs(WPOI4-5)), characterized by high oxytocin receptor expression (OXTR(High)), contribute to local-regional metastasis. OXTR(High) CAFs induce a desmoplastic stroma and CCL26 is required for the invasive phenotype of CCR3(+) tumors. Mechanistically, OXTR activates nuclear ERK5 transcription signaling via Gαq and CDC37 to maintain high levels of OXTR and CCL26. ERK5 ablation reprograms the pro-invasive phenotype of OXTR(High) CAFs. Therefore, targeting ERK5 signaling in OXTR(High) CAFs is a potential therapeutic strategy for OSCC patients with WPOI 4-5.
Research Division(s)
PubMed ID
Open Access at Publisher's Site
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Creation Date: 2022-09-07 09:50:58
Last Modified: 2022-09-07 09:55:01
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