Int J Biol Sci 2024; 20(3):818-830. doi:10.7150/ijbs.91786 This issue Cite
Research Paper
1. Institute of Oral Sciences, Chung Shan Medical University, Taichung, Taiwan.
2. Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan.
3. Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
4. Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan.
5. Division of Hematology and Oncology, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan.
6. School of Medicine, Chung Shan Medical University, Taichung, Taiwan.
7. Whole-Genome Research Core Laboratory of Human Diseases, Chang Gung Memorial Hospital, Keelung, Taiwan.
8. Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
# These authors contributed equally to this work.
Insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2), with high affinity to a myriad of RNA transcripts, has been shown to elicit promotive effects on tumorigenesis and metastasis. Yet, the functional involvement of IGF2BP2 in the progression of oral squamous cell carcinoma (OSCC) remains poorly understood. In this study, we showed that IGF2BP2 was upregulated in head and neck cancer, and high levels of IGF2BP2 were associated with poor survival. In in vitro experiments, IGF2BP2 promoted migration and invasion responses of OSCC cells. Moreover, we identified an IGF2BP2-regulated gene, EREG, which functioned as a modulator of OSCC invasion downstream of IGF2BP2. In addition, EREG expression triggered the epithelia-mesenchymal transition (EMT) in OSCC, as evidenced by the observation that knockdown of EREG weakened the induction of EMT mediated by IFG2BP2, and replenishment of EREG favored the EMT in IGF2BP2-depleted cells. Such IGF2BP2-regulated EREG expression, EMT, and cell invasion were dependent on the activation of FAK/Src signaling pathway. Collectively, these findings suggest that EREG, serving as a functional mediator of IGF2BP2-regulated EMT and cell invasion in oral cancer, may be implicated as a potential target for antimetastatic therapies.
Keywords: insulin-like growth factor 2 mRNA binding protein 2, oral squamous cell carcinoma, epithelia-mesenchymal transition