Targeting the MAP kinase pathway in astrocytoma cells using a recombinant anthrax lethal toxin as a way to inhibit cell motility and invasion

  • Authors:
    • Saleh Al-Dimassi
    • Gilbert Salloum
    • Bechara Saykali
    • Oula Khoury
    • Shihui Liu
    • Stephen H. Leppla
    • Ralph Abi-Habib
    • Mirvat El-Sibai
  • View Affiliations

  • Published online on: March 9, 2016     https://doi.org/10.3892/ijo.2016.3431
  • Pages: 1913-1920
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Abstract

Malignant astrocytomas are highly invasive into adjacent and distant regions of the normal brain. Understanding and targeting cancer cell invasion is an important therapeutic approach. Cell invasion is a complex process that replies on many signaling pathways including the mitogen-activated protein (MAP) kinase (MAPK). In many cell lines, the use of MAPK-targeted drugs proved to be a potential method to inhibit cancer cell motility. In the present study, we use a recombinant anthrax lethal toxin (LeTx), which selectively inhibits the MAPK pathway, in order to target invasion. LeTx proved ineffective on cell survival in astrocytoma (as well as normal cells). However, astrocytoma cells that were treated with LeTx showed a significant decrease in cell motility as seen by wound healing as well as random 2D motility in serum. The cells also showed a decrease in invasion across a collagen matrix. The effect of LeTx on cell migration was mediated though the deregulation of Rho GTPases, which play a role in cell motility. Finally, the effect of LeTx on cell migration and Rho GTPases was mimicked by the inhibition of the MAPK pathway. In this study, we describe for the first time the effect of the LeTx on cancer cell motility and invasion not cell survival making it a potentially selective brain tumor invasion inhibitor.
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May-2016
Volume 48 Issue 5

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Al-Dimassi S, Salloum G, Saykali B, Khoury O, Liu S, Leppla SH, Abi-Habib R and El-Sibai M: Targeting the MAP kinase pathway in astrocytoma cells using a recombinant anthrax lethal toxin as a way to inhibit cell motility and invasion. Int J Oncol 48: 1913-1920, 2016.
APA
Al-Dimassi, S., Salloum, G., Saykali, B., Khoury, O., Liu, S., Leppla, S.H. ... El-Sibai, M. (2016). Targeting the MAP kinase pathway in astrocytoma cells using a recombinant anthrax lethal toxin as a way to inhibit cell motility and invasion. International Journal of Oncology, 48, 1913-1920. https://doi.org/10.3892/ijo.2016.3431
MLA
Al-Dimassi, S., Salloum, G., Saykali, B., Khoury, O., Liu, S., Leppla, S. H., Abi-Habib, R., El-Sibai, M."Targeting the MAP kinase pathway in astrocytoma cells using a recombinant anthrax lethal toxin as a way to inhibit cell motility and invasion". International Journal of Oncology 48.5 (2016): 1913-1920.
Chicago
Al-Dimassi, S., Salloum, G., Saykali, B., Khoury, O., Liu, S., Leppla, S. H., Abi-Habib, R., El-Sibai, M."Targeting the MAP kinase pathway in astrocytoma cells using a recombinant anthrax lethal toxin as a way to inhibit cell motility and invasion". International Journal of Oncology 48, no. 5 (2016): 1913-1920. https://doi.org/10.3892/ijo.2016.3431