Cytoplasmic eIF6 promotes OSCC malignant behavior through AKT pathway

细胞质 eIF6 通过 AKT 通路促进 OSCC 恶性行为

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作者:Zechen Zhao #, Weiming Chu #, Yang Zheng #, Chao Wang, Yuemei Yang, Teng Xu, Xueming Yang, Wei Zhang, Xu Ding, Gang Li, Hongchuang Zhang, Junbo Zhou, Jinhai Ye, Heming Wu, Xiaomeng Song, Yunong Wu

Background

Eukaryotic translation initiation factor 6 (eIF6), also known as integrin β4 binding protein, is involved in ribosome formation and mRNA translation, acting as an anti-association factor. It is also essential for the growth and reproduction of cells, including tumor cells. Yet, its role in oral squamous cell carcinoma (OSCC) remains unclear.

Conclusion

These results demonstrated that eIF6 could be a new therapeutic target in OSCC, thus providing a new basis for the prognosis of OSCC patients in the future. Video abstract.

Methods

The expression characteristics of eIF6 in 233 samples were comprehensively analyzed by immunohistochemical staining (IHC). Effects of eIF6 over-expression and knockdown on cell proliferation, migration and invasion were determined by CCK-8, wound healing and Transwell assays. Western blot, immunofluorescence (IF) and co-immunoprecipitation (co-IP) were performed for mechanical verification.

Results

We found that cytoplasmic eIF6 was abnormally highly expressed in OSCC tissues, and its expression was associated with tumor size and the clinical grade. Amplification of eIF6 promoted the growth, migration and invasion capabilities of OSCC cell lines in vitro and tumor growth in vivo. Through Western blot analysis, we further discovered that eIF6 significantly promotes epithelial-mesenchymal transformation (EMT) in OSCC cells, while depletion of eIF6 can reverse this process. Mechanistically, eIF6 promoted tumor progression by activating the AKT signaling pathway. By performing co-immunoprecipitation, we discovered a direct interaction between endogenous eIF6 and AKT protein in the cytoplasm.

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