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Radiother Oncol. 2013 Sep;108(3):479-83. doi: 10.1016/j.radonc.2013.06.033. Epub 2013 Jul 25.

EGFR overexpressing cells and tumors are dependent on autophagy for growth and survival.

Author information

1
Maastricht Radiation Oncology (MaastRO) Lab, GROW - School for Oncology and Developmental Biology, Maastricht University, Maastricht, The Netherlands.

Abstract

BACKGROUND AND PURPOSE:

The epidermal growth factor receptor (EGFR) is overexpressed, amplified or mutated in various human epithelial tumors, and is associated with tumor aggressiveness and therapy resistance. Autophagy activation provides a survival advantage for cells in the tumor microenvironment. In the current study, we assessed the potential of autophagy inhibition (using chloroquine (CQ)) in treatment of EGFR expressing tumors.

MATERIAL AND METHODS:

Quantitative PCR, immunohistochemistry, clonogenic survival, proliferation assays and in vivo tumor growth were used to assess this potential.

RESULTS:

We show that EGFR overexpressing xenografts are sensitive to CQ treatment and are sensitized to irradiation by autophagy inhibition. In HNSSC xenografts, a correlation between EGFR and expression of the autophagy marker LC3b is observed, suggesting a role for autophagy in EGFR expressing tumors. This observation was substantiated in cell lines, showing high EGFR expressing cells to be more sensitive to CQ addition as reflected by decreased proliferation and survival. Surprisingly high EGFR expressing cells display a lower autophagic flux.

CONCLUSIONS:

The EGFR high expressing cells and tumors investigated in this study are highly dependent on autophagy for growth and survival. Inhibition of autophagy may therefore provide a novel treatment opportunity for EGFR overexpressing tumors.

KEYWORDS:

Autophagy; Chloroquine; EGFR; Irradiation

PMID:
23891088
DOI:
10.1016/j.radonc.2013.06.033
[Indexed for MEDLINE]

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