FNDC3B promotes epithelial-mesenchymal transition in tongue squamous cell carcinoma cells in a hypoxic microenvironment.

Zhaoming Zhong,Chuanzheng Sun,Jin Liang,Minjie He,Weiqing Liu,Xiao Chen,Min Hong,Hongxing Zhang,Yuanyuan Xu,Change Gao

doi:10.3892/or.2018.6231

Abstract

The primary reasons for the treatment failure of patients with oral tongue squamous cell carcinoma (OTSCC) are metastasis and tumor recurrence. Identifying the exact mechanisms underlying metastasis is a key point in improving patient prognosis. It has been reported that a hypoxic microenvironment plays an important role during the metastasis of malignancies. We found that the expression of fibronectin type III domain containing 3B (FNDC3B) is positively correlated with lymph node metastasis and advanced cTNM stage of OTSCC by IHC assay and correlation analysis. Furthermore, we found that knockdown of FNDC3B could suppress the migratory and invasive abilities of OTSCC cells. In addition, treating OTSCC cells with CoCl2 (a hypoxia mimetic agent) upregulated the mRNA and protein expression of FNDC3B via HIF-1α. Moreover, the resultant increase in FNDC3B expression significantly induced epithelial-mesenchymal transition (EMT) in OTSCC cells. The present study elucidated the important role played by FNDC3B in OTSCC metastasis and indicates FNDC3B as a potential target for the treatment of OTSCC metastasis. However, many questions remain to be explored.

Highlights

Head and neck squamous cell carcinoma (HNSCC) accounts for 90% of all head and neck cancers, and is the sixth mostKey words: tongue squamous cell carcinoma, fibronectin type III domain containing 3B (FNDC3B), epithelialmesenchymal transition, metastasis, hypoxia-inducible factor 1α common malignancy worldwide [1]
Analyses using mouse embryonic fibroblasts (MEFs) revealed that loss of FNDC3B suppressed cell adhesion, migration and proliferation [10]. These results suggest that FNDC3B has important roles in cell adhesion, migration and proliferation, which raised the question as to whether FNDC3B regulates the invasion and metastasis of cancer cells and promoted us to investigate its role in the metastasis of cancer cells
To identify the molecules involved in lymph node metastasis of human oral tongue squamous cell carcinoma (OTSCC), a microarray meta-analysis was performed to compare all genes across 5 different datasets

Summary

Introduction

Head and neck squamous cell carcinoma (HNSCC) accounts for 90% of all head and neck cancers, and is the sixth most. FNDC3B (fibronectin type III domain containing 3B), named FAD104, was found to be upregulated in tongue cancer through a web-based bioinformatic meta-analysis (oncomine). The fibronectin type III (FNIII) domains act as a scoffold and can integrate with different proteins, which plays an important role in cell adhesion and growth signaling [8]. Analyses using mouse embryonic fibroblasts (MEFs) revealed that loss of FNDC3B suppressed cell adhesion, migration and proliferation [10]. These results suggest that FNDC3B has important roles in cell adhesion, migration and proliferation, which raised the question as to whether FNDC3B regulates the invasion and metastasis of cancer cells and promoted us to investigate its role in the metastasis of cancer cells. There is little research concerning its biological functions, in the metastasis of tongue squamous cell carcinoma

Methods

Results

Conclusion