Oncotarget

Research Papers:

Pharmacological induction of cell surface GRP78 contributes to apoptosis in triple negative breast cancer cells

Annat Raiter _, Rinat Yerushalmi and Britta Hardy

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Oncotarget. 2014; 5:11452-11463. https://doi.org/10.18632/oncotarget.2576

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Abstract

Annat Raiter1,*, Rinat Yerushalmi2,*, Britta Hardy1

1Felsenstein Medical Research Center, Tel Aviv University School of Medicine, Rabin Medical Center, Petach Tikva, 49100, Israel

2Oncology Institute, Rabin Medical Center, Petach Tikva, 49100, Israel

*These authors contributed equally to this work

Correspondence to:

Britta Hardy, e-mail: bhardy@post.tau.ac.il

Keywords: triple negative breast cancer cells, drug induced cell surface GRP78, apoptosis

Received: July 16, 2014     Accepted: October 05, 2014     Published: October 24, 2014

ABSTRACT

Breast cancer tumor with triple-negative receptors (estrogen, progesterone and Her 2, receptors) is the most aggressive and deadly subtype, with high rates of disease recurrence and poor survival.

Here, we show that induction in cell surface GRP78 by doxorubicin and tunicamycin was associated with CHOP/GADD153 upregulation and increase in apoptosis in triple negative breast cancer tumor cells.

GRP78 is a major regulator of the stress induced unfolded protein response pathway and CHOP/GADD153 is a pro-apoptotic transcription factor associated exclusively with stress induced apoptosis.

The blocking of cell surface GRP78 by anti-GRP78 antibody prevented apoptosis, suggesting that induction of cell surface GRP78 by doxorubicin and tunicamycin is required for apoptosis.

A better understanding of stress induction of apoptotic signaling in triple negative breast cancer cells may help to define new therapeutic strategies.


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