A high level
protein synthesis is one of the characteristics of
cancer cells. The aim of this study is to show the contribution of eukaryotic
elongation factor 2 (eEF2), which plays an essential role in the
polypeptide chain elongation step, in the
tumorigenesis of
gastrointestinal cancers. In the present study, we demonstrated by using immunohistochemistry that eEF2
protein was overexpressed in 92.9% (13 of 14) of gastric and 91.7% (22 of 24) of
colorectal cancers. No mutations were found in any of the exons of the eEF2 gene in six gastric and six
colorectal cancers. Knockdown of eEF2 by eEF2-specific
short-hairpin RNA (shEF2) inhibited
cancer cell growth in two
gastric cancer cell lines, AZ-521 and MKN28, and one
colon cancer cell line, SW620. Flow cytometric analysis showed that knockdown of eEF2 induced G2/M arrest and resulted in inactivation of Akt and cdc2 (a G2/M regulator) and activation of eEF2
kinase (a negative regulator of eEF2) in these
cancer cells. Conversely, forced expression of eEF2 in AZ-521 cells significantly enhanced the cell growth through promotion of G2/M progression in cell cycle, activated Akt and cdc2, and inactivated eEF2
kinase. Furthermore, forced expression of eEF2 in these
cancer cells enhanced in vivo tumorigenicity in a mouse xenograft model. These results showed that overexpressed eEF2 in
gastrointestinal cancers promoted G2/M progression and enhanced their cell growth in vitro and in vivo. These results also suggested a novel linkage between translational elongation and cell cycle mechanisms, implying that the linkage might play an important role to orchestrate the deregulated translation and cell cycle mechanisms for promotion of the development of
gastrointestinal cancers.