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

Annat Raiter, Rinat Yerushalmi, Britta Hardy

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)11452-11463
Number of pages12
JournalOncotarget
Volume5
Issue number22
DOIs
StatePublished - 2014
Externally publishedYes

Keywords

  • Apoptosis
  • Drug induced cell surface GRP78
  • Triple negative breast cancer cells

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