Akt/PKB promotes cancer cell invasion via increased motility and metalloproteinase production

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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-kappaB 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.
Publisher
FEDERATION AMER SOC EXP BIOL
Issue Date
2001
Language
English
Article Type
Article
Keywords

NF-KAPPA-B; PROTEIN-KINASE-B; AKT PROTOONCOGENE; TRANSCRIPTION FACTOR; ACTIN ORGANIZATION; SURVIVAL SIGNALS; IV COLLAGENASE; METASTASIS; ACTIVATION; RAC

Citation

FASEB JOURNAL, v.15, no.11, pp.1953 - 1962

ISSN
0892-6638
DOI
10.1096/fj.01-0198com
URI
http://hdl.handle.net/10203/80655
Appears in Collection
BS-Journal Papers(저널논문)
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