Cytoplasmic eIF6 Promotes OSCC Malignant Behavior Through AKT Pathway

作者：Zechen Zhao, Weming Chu, Yang Zheng, Chao Wang, Yuemei Yang, Xu Teng, Xueming Yang, Wei Zhang, Xu Ding, Gang Li, Hongchuang Zhang, Junbo Zhou, Jinhai Ye, Heming Wu, Xiaomeng Song, Yunong Wu · 发表于：Research Square · 年份：2021 · DOI：10.21203/rs.3.rs-845810/v1 · 被引用次数：1 · 研究领域：Polyamine Metabolism and Applications、Cancer-related molecular mechanisms research、Genomics, phytochemicals, and oxidative stress

Abstract Background: Eukaryotic translation initiation factor 6 (eIF6), also known as integrin β4 binding protein, is involved in the formation and translation of ribosomes and acts 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. Methods: The expression characteristics of eIF6 in 233 samples were comprehensively analyzed by immumohistochemical 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 mechanism 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 promotes 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. Conclusions: Th...