Open Access

Different functions of AKT1 and AKT2 in molecular pathways, cell migration and metabolism in colon cancer cells

  • Authors:
    • Sara Häggblad Sahlberg
    • Anja C. Mortensen
    • Jakob Haglöf
    • Mikael K.R. Engskog
    • Torbjörn Arvidsson
    • Curt Pettersson
    • Bengt Glimelius
    • Bo Stenerlöw
    • Marika Nestor
  • View Affiliations

  • Published online on: November 18, 2016     https://doi.org/10.3892/ijo.2016.3771
  • Pages: 5-14
  • Copyright: © Häggblad Sahlberg et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

AKT is a central protein in many cellular pathways such as cell survival, proliferation, glucose uptake, metabolism, angiogenesis, as well as radiation and drug response. The three isoforms of AKT (AKT1, AKT2 and AKT3) are proposed to have different physiological functions, properties and expression patterns in a cell type-dependent manner. As of yet, not much is known about the influence of the different AKT isoforms in the genome and their effects in the metabolism of colorectal cancer cells. In the present study, DLD-1 isogenic AKT1, AKT2 and AKT1/2 knockout colon cancer cell lines were used as a model system in conjunction with the parental cell line in order to further elucidate the differences between the AKT isoforms and how they are involved in various cellular pathways. This was done using genome wide expression analyses, metabolic profiling and cell migration assays. In conclusion, downregulation of genes in the cell adhesion, extracellular matrix and Notch-pathways and upregulation of apoptosis and metastasis inhibitory genes in the p53-pathway, confirm that the knockout of both AKT1 and AKT2 will attenuate metastasis and tumor cell growth. This was verified with a reduction in migration rate in the AKT1 KO and AKT2 KO and most explicitly in the AKT1/2 KO. Furthermore, the knockout of AKT1, AKT2 or both, resulted in a reduction in lactate and alanine, suggesting that the metabolism of carbohydrates and glutathione was impaired. This was further verified in gene expression analyses, showing downregulation of genes involved in glucose metabolism. Additionally, both AKT1 KO and AKT2 KO demonstrated an impaired fatty acid metabolism. However, genes were upregulated in the Wnt and cell proliferation pathways, which could oppose this effect. AKT inhibition should therefore be combined with other effectors to attain the best effect.
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January-2017
Volume 50 Issue 1

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Spandidos Publications style
Häggblad Sahlberg S, Mortensen AC, Haglöf J, Engskog MK, Arvidsson T, Pettersson C, Glimelius B, Stenerlöw B and Nestor M: Different functions of AKT1 and AKT2 in molecular pathways, cell migration and metabolism in colon cancer cells. Int J Oncol 50: 5-14, 2017.
APA
Häggblad Sahlberg, S., Mortensen, A.C., Haglöf, J., Engskog, M.K., Arvidsson, T., Pettersson, C. ... Nestor, M. (2017). Different functions of AKT1 and AKT2 in molecular pathways, cell migration and metabolism in colon cancer cells. International Journal of Oncology, 50, 5-14. https://doi.org/10.3892/ijo.2016.3771
MLA
Häggblad Sahlberg, S., Mortensen, A. C., Haglöf, J., Engskog, M. K., Arvidsson, T., Pettersson, C., Glimelius, B., Stenerlöw, B., Nestor, M."Different functions of AKT1 and AKT2 in molecular pathways, cell migration and metabolism in colon cancer cells". International Journal of Oncology 50.1 (2017): 5-14.
Chicago
Häggblad Sahlberg, S., Mortensen, A. C., Haglöf, J., Engskog, M. K., Arvidsson, T., Pettersson, C., Glimelius, B., Stenerlöw, B., Nestor, M."Different functions of AKT1 and AKT2 in molecular pathways, cell migration and metabolism in colon cancer cells". International Journal of Oncology 50, no. 1 (2017): 5-14. https://doi.org/10.3892/ijo.2016.3771