Oncotarget

Research Papers:

The double benefit of Spalax p53: surviving underground hypoxia while defying lung cancer cells in vitro via autophagy and caspase-dependent cell death

Martin Ellis, Orly Stern and Osnat Ashur-Fabian _

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Oncotarget. 2016; 7:63242-63251. https://doi.org/10.18632/oncotarget.11443

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Abstract

Martin Ellis1,2, Orly Stern1, Osnat Ashur-Fabian1,2,3

1Translational Hemato-Oncology Laboratory, Hematology Institute and Blood Bank, Meir Medical Center, Kfar-Saba, 4428164, Israel

2Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, 69978, Israel

3The Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, 69978, Israel

Correspondence to:

Osnat Ashur-Fabian, email: [email protected]

Keywords: spalax, p53, lung cancer, autophagy, caspases

Received: June 09, 2016     Accepted: August 15, 2016     Published: August 20, 2016

ABSTRACT

The blind subterranean mole rat, Spalax ehrenbergi, is a model organism for hypoxia tolerance. This superspecies have adapted to severe environment by altering an array of hypoxia-mediated genes, among which an alteration in the p53 DNA binding domain (corresponding to R174K in humans) that hinders its transcriptional activity towards apoptotic genes. It is well accepted that apoptosis is not the only form of programmed cell death and that mechanisms that depend on autophagy are also involved. In the current work we have extended our research and investigated the possibility that Spalax p53 can activate autophagy. Using two complementary assays, we have established that over-expression of the Spalax p53 in p53-null cells (human lung cancer cells, H1299), potently induces autophagy. As Spalax is considered highly resistant to cancer, we further studied the relative contribution of autophagy on the outcome of H1299 cells, following transfection with Spalax p53. Results indicate that Spalax p53 acts as a tumor suppressor in lung cancer cells, inducing cell death that involves autophagy and caspases and inhibiting cell number, which is exclusively caspase-dependent. To conclude, the Spalax p53 protein was evolutionary adapted to survive severe underground hypoxia while retaining the ability to defy lung cancer.


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