Oncotarget

Research Papers:

The pro-apoptotic paradox: the BH3-only protein Bcl-2 interacting killer (Bik) is prognostic for unfavorable outcomes in breast cancer

Vrajesh Pandya _, Darryl Glubrecht, Larissa Vos, John Hanson, Sambasivarao Damaraju, John Mackey, Judith Hugh and Ing Swie Goping

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Oncotarget. 2016; 7:33272-33285. https://doi.org/10.18632/oncotarget.8924

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Abstract

Vrajesh Pandya1, Darryl Glubrecht2, Larissa Vos2, John Hanson2, Sambasivarao Damaraju3, John Mackey2, Judith Hugh3, Ing Swie Goping1,2

1Department of Biochemistry, University of Alberta, Edmonton, Alberta T6G 2H7, Canada

2Department of Oncology, University of Alberta, Edmonton, Alberta T6G 2H7, Canada

3Laboratory Medicine and Pathology, University of Alberta, Edmonton, Alberta T6G 2H7, Canada

Correspondence to:

Ing Swie Goping, e-mail: igoping@ualberta.ca

Keywords: breast cancer, BH3-only proteins, Bcl-2 interacting killer, BiK, autophagy

Received: March 02, 2016    Accepted: April 10, 2016    Published: April 22, 2016

ABSTRACT

Breast cancer is the leading cause of cancer-associated deaths in women worldwide. Clinical biomarkers give information on disease progression and identify relevant biological pathways. A confounding factor that uncouples markers from disease outcome is the ability of tumor cells to mutate and evade clinical intervention. Therefore, we focussed on apoptotic genes that modulate tumor regression. Using gene and tissue microarray analyses, we identified an association of Bcl-2 interacting killer (Bik) with poor breast cancer prognosis. Bik prognostic ability was independent of Estrogen Receptor/Progesterone Receptor and Her2 status. Additionally, Bik was independent of anti-apoptotic Bcl-2, Bcl-xL, Mcl-1 and Bcl-w suggesting a complex mechanism of tumor promotion identified by Bik high tumors. Bik also stimulates autophagy, which can contribute to enhanced tumor fitness. We found a significant association between the autophagy marker ATG5 and Bik. Combined high expression level of ATG5 and Bik was a stronger predictor of outcome than either alone. Thus, our study identifies Bik as a novel, independent prognostic biomarker for poor outcomes in breast cancer and suggests that Bik-mediated autophagy contributes to disease recurrence.


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