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* National Creative Research Initiative Center for Cell Growth Regulation and
Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Taejon 305–701, Korea
1Correspondence: Department of Biological Sciences, Korea Advanced Institute of Science and Technology, 373–1 Kusong-Dong, Yusong, Taejon 305–701, Korea. E-mail: jchung{at}mail.kaist.ac.kr
The Akt/protein kinase B (PKB) serine/threonine kinase is well known as
an important mediator of many cell survival signaling pathways. Here,
we demonstrate for the first time a major role of Akt/PKB in the cell
invasion properties of the highly metastatic cell line HT1080. Using
confocal microscopic analyses of live samples, we found Akt/PKB to be
localized in the leading edge membrane area of migrating HT1080 cells.
This localization was dependent on phosphoinositide 3-kinase and
required the lipid binding ability of the phosphoinositide binding
pleckstrin homology domain of Akt/PKB. We examined the possible
function of Akt/PKB in HT1080 invasion. Surprisingly, Akt/PKB potently
promoted HT1080 invasion, by increasing cell motility and matrix
metalloproteinase-9 (MMP-9) production, in a manner highly dependent on
its kinase activity and membrane-translocating ability. The increase in
MMP-9 production was mediated by activation of nuclear factor-
B
transcriptional activity by Akt/PKB. However, Akt/PKB did not affect
the cell-cell or cell-matrix adhesion properties of HT1080. Our
findings thus establish Akt/PKB as a major factor in the invasive
abilities of cancer cells.—Kim, D., Kim, S., Koh, H., Yoon, S.-O.,
Chung, A.-S., Cho, K. S., Chung, J. Akt/PKB promotes cancer cell
invasion via increased motility and metalloproteinase production.
Key Words: cell migration • PI3 kinase • NF-B • MMP-9 • tumor invasion
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