EIF4E is the rate-limiting factor in the mRNA translation of specific set of oncogenes. Snail is the core transcription factor of epithelial-mesenchymal transition (EMT), a key step of cancer metastasis. The connection between the two oncoproteins has not been well established in the human cancer tissues and in nasopharyngeal carcinoma (NPC). Here we showed that the positive correlative over-expression was seen between eIF4E and Snail in NPC tissues, and the expression was significantly higher in the metastatic NPC than in the un-metastatic NPC. In NPC cells, eIF4E knockdown significantly reduced Snail mRNA and protein levels, increased the mRNA level of E-cad (a direct downstream gene of Snail and a negative EMT marker), attenuated the invasive ability of the cells, and sensitized the cells to cisplatin in invasion. In contrast, enforced the expression of eIF4E significantly increased Snail mRNA and protein levels, and promoted the invasive ability in NPC cells. Under the condition of the high eIF4E expression, Snail knockdown significantly increased E-cad mRNA level and weaken the invasive ability of NPC cells. Finally, eIF4E directly bound Snail mRNA for translation initiation displayed by the RIP assay. Therefore, the results firstly suggested that eIF4E enhanced the Snail expression in both transcription and translation manner in human cancer tissues and targeting the eIF4E/Snail axis might intervene with the EMT and metastasis of NPC. This finding provided a new clue for further understanding the metastatic mechanism of human cancers and for preventing and treating NPC metastasis.
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This work was funded by the Natural Science Fund of Guangdong Province (2015A030313519), the National Natural Science Fund of China (81572566) and the Science and Technology Planning Project of Guangdong Province (2016A020215146).
Conflict of Interest
Authors Yunhong Yao, Tianyun Pang, Ying Cheng, Weiwei Yong, Haixian Kang, Yi Zhao, Sen Wang and Xinrong Hu declare that they have no conflict of interest.
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Yao, Y., Pang, T., Cheng, Y. et al. Positive Correlative over-Expression between eIF4E and Snail in Nasopharyngeal Carcinoma Promotes its Metastasis and Resistance to Cisplatin. Pathol. Oncol. Res. 26, 1639–1649 (2020). https://doi.org/10.1007/s12253-019-00733-x