FERMT2 upregulation in CAFs enhances EMT of OSCC and M2 macrophage polarization

Author:

Ma Xiangrui12ORCID,Zhao Dan3,Liu Shan4,Zuo Jinhua2,Wang Wenlong2ORCID,Wang Fang2,Li Yourui5,Ding Zhangfan16,Wang Jing7ORCID,Wang Xiaoyi16ORCID

Affiliation:

1. State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, West China College of Stomatology Sichuan University Chengdu China

2. Department of Oral and Maxillofacial Surgery Binzhou Medical University Hospital Binzhou China

3. Department of Oral and Maxillofacial Surgery The Affiliated Stomatological Hospital of Southwest Medical University Luzhou China

4. Department of Oral and Maxillofacial Surgery The First Affiliated Hospital of Zhengzhou University Zhengzhou China

5. Department of Prosthodontics Binzhou Medical University Hospital Binzhou China

6. Department of Oral and Maxillofacial Surgery, West China School of Stomatology Sichuan University Chengdu China

7. Department of Oral Medicine Binzhou Medical University Hospital Binzhou China

Abstract

AbstractObjectivesFERMT2 upregulation was associated with malignant tumor behaviors, including epithelial‐to‐mesenchymal (EMT). This study aimed to characterize the expression profile of FERMT2 in oral squamous cell carcinoma (OSCC) and to explore its involvement in the tumor microenvironment sculptured by oral cancer‐associated fibroblasts (OCAFs).MaterialsPrevious bulk‐seq (TCGA‐HNSC) and single‐cell RNA‐seq data sets were retrieved for bioinformatic analysis. Human OSCC lines SCC15 and CAL27, primary normal oral fibroblasts (NOFs), OCAFs, and THP‐1 cells were used for intro studies.ResultsFERMT2 expression was significantly higher in CAFs compared with OSCC tumor cells and normal fibroblasts. Higher FERMT2 expression might independently predict unfavorable disease‐specific survival (DSS) in patients with OSCC. Knockdown of FERMT2 suppressed the expression and secretion of IGFBP7, SPARC, TIMP3, COL4A1, and IGFBP4 in OCAFs. OCAFs with FERMT2 knockdown had significantly weakened capability to induce the invasion of OSCC cells and the expression of mesenchymal markers. FERMT2 knockdown impaired the inducing effect of OCAFs on the migration of M0 macrophages and the expression of M2 macrophage markers.ConclusionsFERMT2 could modulate the production and secretion of IGFBP7, SPARC, COL4A1, and IGFBP4 in OCAFs, thereby inducing the EMT of OSCC and M2 macrophage polarization.

Funder

Natural Science Foundation of Shandong Province

Publisher

Wiley

Subject

General Dentistry,Otorhinolaryngology

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