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Sci. Signal., 13 October 2009
Vol. 2, Issue 92, p. ra62
[DOI: 10.1126/scisignal.2000356]


Editor's Summary

Balance Is Everything
Members of the Akt family of protein kinases, which are activated by growth factor signaling, have been implicated in human cancer; however, the different Akt isoforms appear to play distinct roles. Iliopoulos et al. used cells containing only a single Akt isoform—or cells in which the abundance of one or two of the three Akt isoforms was selectively reduced—to explore their specific contributions to tumor induction and invasiveness. They found that growth factor stimulation of the different isoforms led to distinct changes in the abundance of microRNAs, a class of molecules that regulate gene expression and can thereby promote or inhibit oncogenesis. Intriguingly, the effects of Akt signaling on the abundance of the miR-200 family of microRNAs—and thereby on the induction of a metastatic phenotype in human breast cancer cells—appeared to depend on the balance in abundance or activity of Akt1 and Akt2 rather than on overall Akt signaling per se.

Citation: D. Iliopoulos, C. Polytarchou, M. Hatziapostolou, F. Kottakis, I. G. Maroulakou, K. Struhl, P. N. Tsichlis, MicroRNAs Differentially Regulated by Akt Isoforms Control EMT and Stem Cell Renewal in Cancer Cells. Sci. Signal. 2, ra62 (2009).

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Post-transcriptional Regulation of Human Breast Cancer Cell Proteome by Unliganded Estrogen Receptor {beta} via microRNAs.
G. Nassa, R. Tarallo, G. Giurato, M. R. De Filippo, M. Ravo, F. Rizzo, C. Stellato, C. Ambrosino, M. Baumann, N. Lietzen, et al. (2014)
Mol. Cell. Proteomics 13, 1076-1090
   Abstract »    Full Text »    PDF »
Akt2 Deficiency Protects from Acute Lung Injury via Alternative Macrophage Activation and miR-146a Induction in Mice.
E. Vergadi, K. Vaporidi, E. E. Theodorakis, C. Doxaki, E. Lagoudaki, E. Ieronymaki, V. I. Alexaki, M. Helms, E. Kondili, B. Soennichsen, et al. (2014)
J. Immunol. 192, 394-406
   Abstract »    Full Text »    PDF »
Epigenetic modulation of the miR-200 family is associated with transition to a breast cancer stem-cell-like state.
Y.-Y. Lim, J. A. Wright, J. L. Attema, P. A. Gregory, A. G. Bert, E. Smith, D. Thomas, A. F. Lopez, P. A. Drew, Y. Khew-Goodall, et al. (2013)
J. Cell Sci. 126, 2256-2266
   Abstract »    Full Text »    PDF »
PKB/Akt-Dependent Regulation of Cell Motility.
G. Xue and B. A. Hemmings (2013)
J Natl Cancer Inst 105, 393-404
   Abstract »    Full Text »    PDF »
The isolation and characterization of renal cancer initiating cells from human Wilms' tumour xenografts unveils new therapeutic targets.
N. Pode-Shakked, R. Shukrun, M. Mark-Danieli, P. Tsvetkov, S. Bahar, S. Pri-Chen, R. S. Goldstein, E. Rom-Gross, Y. Mor, E. Fridman, et al. (2013)
EMBO Mol Med. 5, 18-37
   Abstract »    Full Text »    PDF »
Epithelial-mesenchymal transitions: insights from development.
J. Lim and J. P. Thiery (2012)
Development 139, 3471-3486
   Abstract »    Full Text »    PDF »
Distinct roles of AKT isoforms in regulating {beta}1-integrin activity, migration, and invasion in prostate cancer.
R. Virtakoivu, T. Pellinen, J. K. Rantala, M. Perala, and J. Ivaska (2012)
Mol. Biol. Cell 23, 3357-3369
   Abstract »    Full Text »    PDF »
MicroRNA-regulated gene networks during mammary cell differentiation are associated with breast cancer.
E. Aydogdu, A. Katchy, E. Tsouko, C.-Y. Lin, L.-A. Haldosen, L. Helguero, and C. Williams (2012)
Carcinogenesis 33, 1502-1511
   Abstract »    Full Text »    PDF »
Akt1 and Akt2 protein kinases differentially contribute to macrophage polarization.
A. Arranz, C. Doxaki, E. Vergadi, Y. Martinez de la Torre, K. Vaporidi, E. D. Lagoudaki, E. Ieronymaki, A. Androulidaki, M. Venihaki, A. N. Margioris, et al. (2012)
PNAS 109, 9517-9522
   Abstract »    Full Text »    PDF »
The protein kinase Akt1 regulates the interferon response through phosphorylation of the transcriptional repressor EMSY.
S. A. Ezell, C. Polytarchou, M. Hatziapostolou, A. Guo, I. Sanidas, T. Bihani, M. J. Comb, G. Sourvinos, and P. N. Tsichlis (2012)
PNAS 109, E613-E621
   Abstract »    Full Text »    PDF »
TGF-{beta}-induced activation of mTOR complex 2 drives epithelial-mesenchymal transition and cell invasion.
S. Lamouille, E. Connolly, J. W. Smyth, R. J. Akhurst, and R. Derynck (2012)
J. Cell Sci. 125, 1259-1273
   Abstract »    Full Text »    PDF »
FOSL1 Is Integral to Establishing the Maternal-Fetal Interface.
L. N. Kent, M. A. K. Rumi, K. Kubota, D.-S. Lee, and M. J. Soares (2011)
Mol. Cell. Biol. 31, 4801-4813
   Abstract »    Full Text »    PDF »
Tumor Progression Locus 2 Mediates Signal-Induced Increases in Cytoplasmic Calcium and Cell Migration.
M. Hatziapostolou, G. Koukos, C. Polytarchou, F. Kottakis, O. Serebrennikova, A. Kuliopulos, and P. N. Tsichlis (2011)
Science Signaling 4, ra55
   Abstract »    Full Text »    PDF »
Angiopoietin-2, an Angiogenic Regulator, Promotes Initial Growth and Survival of Breast Cancer Metastases to the Lung through the Integrin-linked Kinase (ILK)-AKT-B Cell Lymphoma 2 (Bcl-2) Pathway.
Y. Imanishi, B. Hu, G. Xiao, X. Yao, and S.-Y. Cheng (2011)
J. Biol. Chem. 286, 29249-29260
   Abstract »    Full Text »    PDF »
Akt2 Regulates All Akt Isoforms and Promotes Resistance to Hypoxia through Induction of miR-21 upon Oxygen Deprivation.
C. Polytarchou, D. Iliopoulos, M. Hatziapostolou, F. Kottakis, I. Maroulakou, K. Struhl, and P. N. Tsichlis (2011)
Cancer Res. 71, 4720-4731
   Abstract »    Full Text »    PDF »
Nonredundant Functions for Akt Isoforms in Astrocyte Growth and Gliomagenesis in an Orthotopic Transplantation Model.
R. Endersby, X. Zhu, N. Hay, D. W. Ellison, and S. J. Baker (2011)
Cancer Res. 71, 4106-4116
   Abstract »    Full Text »    PDF »
Inducible formation of breast cancer stem cells and their dynamic equilibrium with non-stem cancer cells via IL6 secretion.
D. Iliopoulos, H. A. Hirsch, G. Wang, and K. Struhl (2011)
PNAS 108, 1397-1402
   Abstract »    Full Text »    PDF »
Small molecule inhibition of phosphatidylinositol-3,4,5-triphosphate (PIP3) binding to pleckstrin homology domains.
B. Miao, I. Skidan, J. Yang, A. Lugovskoy, M. Reibarkh, K. Long, T. Brazell, K. A. Durugkar, J. Maki, C. V. Ramana, et al. (2010)
PNAS 107, 20126-20131
   Abstract »    Full Text »    PDF »
Oncogenes and Tumor Suppressor Genes.
E. Y. H. P. Lee and W. J. Muller (2010)
Cold Spring Harb Perspect Biol 2, a003236
   Abstract »    Full Text »    PDF »
The ZEB/miR-200 feedback loop--a motor of cellular plasticity in development and cancer?.
S. Brabletz and T. Brabletz (2010)
EMBO Rep. 11, 670-677
   Abstract »    Full Text »    PDF »
Distinct Biological Roles for the Akt Family in Mammary Tumor Progression.
R. L. Dillon and W. J. Muller (2010)
Cancer Res. 70, 4260-4264
   Abstract »    Full Text »    PDF »

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