MARCKS phosphorylation is modulated by a peptide mimetic of MARCKS effector domain leading to increased radiation sensitivity in lung cancer cell lines

Rohrbach,Timothy  D.; Jones,Robert   B.; Hicks,Patricia   H.; Weaver,Alice   N.; Cooper,Tiffiny   S.; Eustace,Nicholas   J.; Yang,Eddy   S.; Jarboe,John   S.; Anderson,Joshua  C.; Willey,Christopher   D.

doi:10.3892/ol.2016.5550

MARCKS phosphorylation is modulated by a peptide mimetic of MARCKS effector domain leading to increased radiation sensitivity in lung cancer cell lines

Authors:
- Timothy D. Rohrbach
- Robert B. Jones
- Patricia H. Hicks
- Alice N. Weaver
- Tiffiny S. Cooper
- Nicholas J. Eustace
- Eddy S. Yang
- John S. Jarboe
- Joshua C. Anderson
- Christopher D. Willey
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Affiliations: Department of Radiation Oncology, University of Alabama at Birmingham, Birmingham, AL 35249, USA
Published online on: December 29, 2016 https://doi.org/10.3892/ol.2016.5550
Pages: 1216-1222
Copyright: © Rohrbach et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Lung cancer is the leading cause of cancer‑associated mortality in the United States. Kinase hyperactivation is a known mechanism of tumorigenesis. The phosphorylation status of the plasma membrane‑associated protein myristoylated alanine rich C‑kinase substrate (MARCKS) effector domain (ED) was previously established as being important in the sensitivity of lung cancer to radiation. Specifically, when MARCKS ED was in a non‑phosphorylated state, lung cancer cells were more susceptible to ionizing radiation and experienced prolonged double‑strand DNA breaks. Additional studies demonstrated that the phosphorylation status of MARCKS ED is important for gene expression and in vivo tumor growth. The present study used a peptide mimetic of MARCKS ED as a therapeutic intervention to modulate MARCKS phosphorylation. Culturing A549, H1792 and H1975 lung cancer cell lines with the MARCKS ED peptide led to reduced levels of phosphorylated MARCKS and phosphorylated Akt serine/threonine kinase 1. Further investigation demonstrated that the peptide therapy was able to reduce lung cancer cell proliferation and increase radiation sensitivity. In addition, the MARCKS peptide therapy was able to prolong double‑strand DNA breaks following ionizing radiation exposure. The results of the present study demonstrate that a peptide mimetic of MARCKS ED is able to modulate MARCKS phosphorylation, leading to an increase in sensitivity to radiation.

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