The DOI matches its Crossref record; 43 of the 43 references it cites were found in a registry or an index.
GRP78/BiP Inhibits Endoplasmic Reticulum BIK and Protects Human Breast Cancer Cells against Estrogen Starvation–Induced Apoptosis
Abstract
The recent development of hormonal therapy that blocks estrogen synthesis represents a major advance in the treatment of estrogen receptor–positive breast cancer. However, cancer cells often acquire adaptations resulting in resistance. A recent report reveals that estrogen starvation–induced apoptosis of breast cancer cells requires BIK, an apoptotic BH3-only protein located primarily at the endoplasmic reticulum (ER). Searching for novel partners that interact with BIK at the ER, we discovered that BIK selectively forms complex with the glucose-regulated protein GRP78/BiP, a major ER chaperone with prosurvival properties naturally induced in the tumor microenvironment. GRP78 overexpression decreases apoptosis of 293T cells induced by ER-targeted BIK. For estrogen-dependent MCF-7/BUS breast cancer cells, overexpression of GRP78 inhibits estrogen starvation–induced BAX activation, mitochondrial permeability transition, and consequent apoptosis. Further, knockdown of endogenous GRP78 by small interfering RNA (siRNA) sensitizes MCF-7/BUS cells to estrogen starvation–induced apoptosis. This effect was substantially reduced when the expression of BIK was also reduced by siRNA. Our results provide the first evidence that GRP78 confers resistance to estrogen starvation–induced apoptosis in human breast cancer cells via a novel mechanism mediated by BIK. These results further suggest that GRP78 expression level in the tumor cells may serve as a prognostic marker for responsiveness to hormonal therapy based on estrogen starvation and that combination therapy targeting GRP78 may enhance efficacy and reduce resistance. [Cancer Res 2007;67(8):3734–40]
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Proapoptotic BAX and BAK: A Requisite Gateway to Mitochondrial Dysfunction and Death
Wei, M. C., Zong, W.-X., Cheng, E. H.-Y., Lindsten, T., Panoutsakopoulou, V., Ross, A. J., Roth, K. A., MacGregor, G. R., Thompson, C. B., & Korsmeyer, S. J. (2001) · Science · doi:10.1126/science.1059108 · Cited by 3,988
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BAX and BAK Regulation of Endoplasmic Reticulum Ca 2+ : A Control Point for Apoptosis
Scorrano, L., Oakes, S. A., Opferman, J. T., Cheng, E. H., Sorcinelli, M. D., Pozzan, T., & Korsmeyer, S. J. (2003) · Science · doi:10.1126/science.1081208 · Cited by 1,385
The glucose-regulated proteins: stress induction and clinical applications
Lee, A. S. (2001) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(01)01908-9 · Cited by 1,032
Self-citationOrchestrating the unfolded protein response in health and disease
Kaufman, R. J. (2002) · Journal of Clinical Investigation · doi:10.1172/jci0216886 · Cited by 1,015
The ER chaperone and signaling regulator GRP78/BiP as a monitor of endoplasmic reticulum stress
Lee, A. S. (2005) · Methods · doi:10.1016/j.ymeth.2004.10.010 · Cited by 991
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Cited by
Glucose-regulated proteins in cancer: molecular mechanisms and therapeutic potential
Lee, A. S. (2014) · Nature Reviews Cancer · doi:10.1038/nrc3701 · Cited by 587
Self-citationLuo, B., & Lee, A. S. (2013) · Oncogene · doi:10.1038/onc.2012.130 · Cited by 560
Self-citationDong, D., Ni, M., Li, J., Xiong, S., Ye, W., Virrey, J. J., Mao, C., Ye, R., Wang, M., Pen, L., et al. (2008) · Cancer Research · doi:10.1158/0008-5472.can-07-2950 · Cited by 375
Self-citationHSPA5 Gene encoding Hsp70 chaperone BiP in the endoplasmic reticulum
Wang, J., Lee, J., Liem, D., & Ping, P. (2017) · Gene · doi:10.1016/j.gene.2017.03.005 · Cited by 308
Chen, J.-Q., Cammarata, P. R., Baines, C. P., & Yager, J. D. (2009) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2009.06.001 · Cited by 264
Metadata
- Authors
- Fu, Y., Li, J., & Lee, A. S.
- Venue
- Cancer Research
- Published
- 2007-04-15
- Volume
- 67
- Issue
- 8
- Pages
- 3734-3740
- ISSN
- 0008-5472 (ISSN-L)
- 1538-7445
- OpenAlex
- W2169879031
- Cited by
- 304
- References
- 43
- FWCI
- 6.57
- Type
- journal article
- Language
- en
- Open access
- closed
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