eEF1A2 activates Akt and stimulates Akt-dependent actin remodeling, invasion and migration.
eEF1A2 (eukaryotic protein elongation factor 1 alpha 2) is a protein translation factor that is likely a human oncogene by virtue of its capacity to transform mammalian cells and its high expression in tumors of the ovary, breast and lung. Here, we show that expression of eEF1A2 is sufficient to stimulate the formation of filopodia in BT549 human breast cancer cells and non-transformed Rat2 cells. Filopodia formation in eEF1A2-expressing cells is dependent on the activity of phosphatidylinositol-3 kinase (PI3K), and the ROCK and Akt kinases. Furthermore, eEF1A2 expression is sufficient to activate Akt in a PI3K-dependent fashion and inactivation of eEF1A2 by short interfering RNA reduces Akt activity. Using breast cancer cell line BT 549, we show that eEF1A2 expression stimulates cell migration and invasion in a largely PI3K- and Akt-dependent manner. These results suggest that eEF1A2 regulates oncogenesis through Akt and PI3K-dependent cytoskeletal remodeling.
Amiri
A
A
Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada.
Noei
F
F
Jeganathan
S
S
Kulkarni
G
G
Pinke
D E
DE
Lee
J M
JM
D000199:Actins / Q000378:metabolism*; D000818:Animals; D001943:Breast Neoplasms / Q000201:enzymology / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D003599:Cytoskeleton / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D004789:Enzyme Activation / Q000502:physiology; D005260:Female; D006801:Humans; D007527:Isoenzymes / Q000502:physiology; D009361:Neoplasm Invasiveness; D020648:Peptide Elongation Factor 1 / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism* / Q000502:physiology; D051381:Rats
D000199:Actins; C503234:EEF1A2 protein, human; D007527:Isoenzymes; D020648:Peptide Elongation Factor 1; D051057:Proto-Oncogene Proteins c-akt