Pharmacological induction of cell surface GRP78 contributes to apoptosis in triple negative breast cancer cells
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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
Britta Hardy, e-mail: [email protected]
Keywords: triple negative breast cancer cells, drug induced cell surface GRP78, apoptosis
Received: July 16, 2014 Accepted: October 05, 2014 Published: October 24, 2014
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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