Aurora-A Mitotic Kinase Induces Endocrine Resistance through Down-Regulation of ERα Expression in Initially ERα+ Breast Cancer Cells
Author
Opyrchal, Mateusz; Salisbury, Jeffrey L.; Zhang, Shuya; McCubrey, James A.; Hawse, John; Goetz, Matthew P.; Lomberk, Gwen A.; Haddad, Tufia; Degnim, Amy; Lange, Carol A.; Ingle, James N.; Galanis, Evanthia; D'Assoro, Antonino B.
Abstract
Development of endocrine resistance during tumor progression represents a major challenge in the management of estrogen receptor alpha (ERα) positive breast tumors and is an area under intense investigation. Although the underlying mechanisms are still poorly understood, many studies point towards the ‘cross-talk’ between ERα and MAPK signaling pathways as a key oncogenic axis responsible for the development of estrogen-independent growth of breast cancer cells that are initially ERα+ and hormone sensitive. In this study we employed a metastatic breast cancer xenograft model harboring constitutive activation of Raf-1 oncogenic signaling to investigate the mechanistic linkage between aberrant MAPK activity and development of endocrine resistance through abrogation of the ERα signaling axis. We demonstrate for the first time the causal role of the Aurora-A mitotic kinase in the development of endocrine resistance through activation of SMAD5 nuclear signaling and down-regulation of ERα expression in initially ERα+ breast cancer cells. This contribution is highly significant for the treatment of endocrine refractory breast carcinomas, because it may lead to the development of novel molecular therapies targeting the Aurora-A/SMAD5 oncogenic axis. We postulate such therapy to result in the selective eradication of endocrine resistant ERαlow/− cancer cells from the bulk tumor with consequent benefits for breast cancer patients.
Date
2014
Citation:
APA:
Opyrchal, Mateusz, & Salisbury, Jeffrey L., & Zhang, Shuya, & McCubrey, James A., & Hawse, John, & Goetz, Matthew P., & Lomberk, Gwen A., & Haddad, Tufia, & Degnim, Amy, & Lange, Carol A., & Ingle, James N., & Galanis, Evanthia, & D'Assoro, Antonino B.. (January 2014).
Aurora-A Mitotic Kinase Induces Endocrine Resistance through Down-Regulation of ERα Expression in Initially ERα+ Breast Cancer Cells.
PLoS ONE,
9(5),
1-
7. Retrieved from
http://hdl.handle.net/10342/5653
MLA:
Opyrchal, Mateusz, and Salisbury, Jeffrey L., and Zhang, Shuya, and McCubrey, James A., and Hawse, John, and Goetz, Matthew P., and Lomberk, Gwen A., and Haddad, Tufia, and Degnim, Amy, and Lange, Carol A., and Ingle, James N., and Galanis, Evanthia, and D'Assoro, Antonino B..
"Aurora-A Mitotic Kinase Induces Endocrine Resistance through Down-Regulation of ERα Expression in Initially ERα+ Breast Cancer Cells". PLoS ONE.
9:5. (1-7),
January 2014.
November 30, 2023.
http://hdl.handle.net/10342/5653.
Chicago:
Opyrchal, Mateusz and Salisbury, Jeffrey L. and Zhang, Shuya and McCubrey, James A. and Hawse, John and Goetz, Matthew P. and Lomberk, Gwen A. and Haddad, Tufia and Degnim, Amy and Lange, Carol A. and Ingle, James N. and Galanis, Evanthia and D'Assoro, Antonino B.,
"Aurora-A Mitotic Kinase Induces Endocrine Resistance through Down-Regulation of ERα Expression in Initially ERα+ Breast Cancer Cells," PLoS ONE 9, no.
5 (January 2014),
http://hdl.handle.net/10342/5653 (accessed
November 30, 2023).
AMA:
Opyrchal, Mateusz, Salisbury, Jeffrey L., Zhang, Shuya, McCubrey, James A., Hawse, John, Goetz, Matthew P., Lomberk, Gwen A., Haddad, Tufia, Degnim, Amy, Lange, Carol A., Ingle, James N., Galanis, Evanthia, D'Assoro, Antonino B..
Aurora-A Mitotic Kinase Induces Endocrine Resistance through Down-Regulation of ERα Expression in Initially ERα+ Breast Cancer Cells. PLoS ONE.
January 2014;
9(5):
1-7.
http://hdl.handle.net/10342/5653. Accessed
November 30, 2023.
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