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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.

Dehydrocostus lactone (DHC) is the main active ingredient extracted from a traditional Chinese medicine called Radix Aucklandiael. A few studies recently showed that DHC has anticancer potential. However, no reports exist as yet on the effects of DHC on colorectal carcinoma (CRC). This study aimed to determine whether and how DHC functions in CRC cells. After treatment with DHC, both Lovo and SW480 cells were significantly inhibited in their proliferation, cell cycle progression, migration, and invasion abilities in a dose-dependent and/or treatment time-dependent manner. Also, DHC significantly increased the apoptosis rate of SW480 cells, but not Lovo cells. The expression of eukaryotic translation initiation factor 4E (eIF4E), which was originally highly expressed in both cells, was significantly decreased by DHC. The inhibition of proliferation, migration, and invasion was significantly attenuated by the ectopic transfection of eIF4E, and was promoted by the knockdown of eIF4E in Lovo cells. To the best of our knowledge, this is the first time it has been shown that DHC suppressed the proliferation, cell cycle progression, antiapoptosis, and migration and invasion capabilities of CRC cells by the downregulation of eIF4E expression. In terms of the overexpression of eIF4E in many cancers, it was speculated that DHC might also play an anticancerous role by suppressing eIF4E expression. This discovery could lay the foundations for advancing our understanding of the anticancerous mechanism of DHC and developing DHC into a novel and effective natural anticancer therapeutic.

Increasing evidence has placed eukaryotic translation initiation factor 4E (eIF4E) at the hub of tumor development and progression. Several studies have reported that eIF4E is over-expressed in cervical cancer; however, the mechanism remains elusive. The results of this study further confirm over-expression of eIF4E in cervical cancer tumors and cell lines, and we have discovered that the transcription of eIF4E is induced by protein E6 of the human papillomavirus (HPV). Moreover, regulation of eIF4E by E6 significantly influences cell proliferation, the cell cycle, migration, and apoptosis. Therefore, eIF4E emerges as a key player in tumor development and progression and a potential target for CC treatment and prevention., (Copyright © 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.)

Eukaryotic translation initiation factor 4E (eIF4E) is involved in integration and amplification of many carcinogenesis signals in tumors. However, it remains unclear whether eIF4E over-expresses in NPC and whether it is associated with the development of NPC. Here, we analyzed the expression state of eIF4E, c-Myc, and MMP9 in 24 nasopharyngitises and 64 nasopharyngeal carcinomas (NPC) tissues and studied the influences of eIF4E on the proliferation and cell cycle in NPC cell lines. The results indicate that eIF4E might over-express in NPC and the over-expression of eIF4E promotes NPC growth and cell cycle progression through enhancing the translational expression of c-Myc and MMP9. The finding certainly adds new knowledge in the understanding of the carcinogenesis of NPC and provides a potential molecular target for the NPC therapy and prevention.