MFI2 upregulation promotes malignant progression through EGF/FAK signaling in oral cavity squamous cell carcinoma

Wei-Chen Yen; Kai-Ping Chang; Cheng-Yi Chen; Yenlin Huang; Ting-Wen Chen; Hsing-Wen Cheng; Jui-Shan Yi; Chun-Chia Cheng; Chih-Ching Wu; Chun-I Wang

doi:10.1186/s12935-023-02956-0

MFI2 upregulation promotes malignant progression through EGF/FAK signaling in oral cavity squamous cell carcinoma

Cancer Cell Int. 2023 Jun 12;23(1):112. doi: 10.1186/s12935-023-02956-0.

Authors

Wei-Chen Yen^#^{1

2}, Kai-Ping Chang^#^{1

2

3}, Cheng-Yi Chen⁴, Yenlin Huang^{5

6}, Ting-Wen Chen^{7

8

9}, Hsing-Wen Cheng¹, Jui-Shan Yi¹, Chun-Chia Cheng¹⁰, Chih-Ching Wu^{1

2

11}, Chun-I Wang¹²

Affiliations

¹ Department of Otolaryngology-Head & Neck Surgery, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
² Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan.
³ College of Medicine, Chang Gung University, Taoyuan, Taiwan.
⁴ Department of Cell Biology and Anatomy, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
⁵ School of Medicine, National Tsing-Hua University, Hsinchu, Taiwan.
⁶ Institute of Stem Cell and Translational Cancer Research, Department of Anatomic Pathology, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan.
⁷ Institute of Bioinformatics and Systems Biology, National Yang Ming Chiao Tung University, Hsinchu, Taiwan.
⁸ Department of Biological Science and Technology, National Yang Ming Chiao Tung University, Hsinchu, Taiwan.
⁹ Center For Intelligent Drug Systems and Smart Bio-devices (IDS2B), National Yang Ming Chiao Tung University, Hsinchu, Taiwan.
¹⁰ Radiation Biology Research Center, Institute for Radiological Research, Chang Gung University, Taoyuan, Taiwan.
¹¹ Department of Medical Biotechnology and Laboratory Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
¹² Department of Biochemistry, School of Medicine, China Medical University, Taichung, Taiwan. yeewang0330@gmail.com.

^# Contributed equally.

Abstract

Oral squamous cell carcinoma (OSCC) is the predominant histological type of the head and neck squamous cell carcinoma (HNSCC). By comparing the differentially expressed genes (DEGs) in OSCC-TCGA patients with copy number variations (CNVs) that we identify in OSCC-OncoScan dataset, we herein identified 37 dysregulated candidate genes. Among these potential candidate genes, 26 have been previously reported as dysregulated proteins or genes in HNSCC. Among 11 novel candidates, the overall survival analysis revealed that melanotransferrin (MFI2) is the most significant prognostic molecular in OSCC-TCGA patients. Another independent Taiwanese cohort confirmed that higher MFI2 transcript levels were significantly associated with poor prognosis. Mechanistically, we found that knockdown of MFI2 reduced cell viability, migration and invasion via modulating EGF/FAK signaling in OSCC cells. Collectively, our results support a mechanistic understanding of a novel role for MFI2 in promoting cell invasiveness in OSCC.