OXTR Stroma Fibroblasts Control the Invasion Pattern of Oral Squamous Cell Carcinoma Via ERK5 Signaling

Overview

Journal Nat Commun

Specialty Biology

Date 2022 Aug 31

PMID 36045118

Authors

Liang Ding

Yong Fu

Nisha Zhu

Mengxiang Zhao

Zhuang Ding

Xiaoxin Zhang

Yuxian Song

Yue Jing

Qian Zhang

Sheng Chen

Xiaofeng Huang

Lorraine A OReilly

John Silke

Qingang Hu

Yanhong Ni

Affiliations

Soon will be listed here.

Abstract

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), characterized by high oxytocin receptor expression (OXTR), contribute to local-regional metastasis. OXTR 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 CAFs. Therefore, targeting ERK5 signaling in OXTR CAFs is a potential therapeutic strategy for OSCC patients with WPOI 4-5.

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