title: Pharmacological induction of cell surface GRP78 contributes to apoptosis in triple negative breast cancer cells.
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.
authors.affiliation: Felsenstein Medical Research Center, Tel Aviv University School of Medicine, Rabin Medical Center, Petach Tikva, 49100, Israel.
authors.forename: Annat
authors.initials: A
authors.lastname: Raiter
authors.affiliation: Oncology Institute, Rabin Medical Center, Petach Tikva, 49100, Israel.
authors.forename: Rinat
authors.initials: R
authors.lastname: Yerushalmi
authors.affiliation: Felsenstein Medical Research Center, Tel Aviv University School of Medicine, Rabin Medical Center, Petach Tikva, 49100, Israel.
authors.forename: Britta
authors.initials: B
authors.lastname: Hardy
mesh_terms: D000818:Animals; D017209:Apoptosis; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D002469:Cell Separation; D004317:Doxorubicin / Q000627:therapeutic use; D000091342:Endoplasmic Reticulum Chaperone BiP; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism; D051379:Mice; D015398:Signal Transduction; D051742:Transcription Factor CHOP / Q000378:metabolism*; D064726:Triple Negative Breast Neoplasms / Q000378:metabolism*; D014415:Tunicamycin / Q000627:therapeutic use; D056811:Unfolded Protein Response
chemical_list: D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; C000717248:Hspa5 protein, mouse; D014415:Tunicamycin; D051742:Transcription Factor CHOP; D004317:Doxorubicin