Title |
The cyclin-like protein, SPY1, regulates the ERα and ERK1/2 pathways promoting tamoxifen resistance
|
---|---|
Published in |
Oncotarget, February 2017
|
DOI | 10.18632/oncotarget.15578 |
Pubmed ID | |
Authors |
Rosa-Maria Ferraiuolo, Janice Tubman, Indrajit Sinha, Caroline Hamm, Lisa Ann Porter |
Abstract |
The Ras/Raf/MEK/ERK pathway conveys growth factor and mitogen signalling to control the phosphorylation of a plethora of substrates regulating proliferation, survival, and migration. The Ras signalling pathway is frequently associated with poor prognosis and drug resistance in various cancers including those of the blood, breast and prostate. Activation of the downstream effector ERK does not always occur via a linear cascade of events; complicating the targeting of this pathway therapeutically. This work describes a novel positive feedback loop where the cell cycle regulatory factor Spy1 (RINGO; gene SPDYA) activates ERK1/2 in a MEK-independent fashion. Spy1 was originally isolated for the ability to stimulate Xenopus oocyte maturation via a MAPK-signalling pathway and is known to override apoptosis triggered by the DNA damage response. We demonstrate that mammalian Spy1-mediated ERK activation increases ligand-independent phosphorylation and activation of estrogen receptor α, correlating with a decrease in tamoxifen sensitivity. This could define a novel druggable mechanism driving proliferation and resistance in select cancers. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
Canada | 3 | 25% |
United States | 3 | 25% |
Austria | 1 | 8% |
Mexico | 1 | 8% |
Unknown | 4 | 33% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 5 | 42% |
Scientists | 4 | 33% |
Practitioners (doctors, other healthcare professionals) | 2 | 17% |
Science communicators (journalists, bloggers, editors) | 1 | 8% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 23 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Master | 6 | 26% |
Student > Ph. D. Student | 5 | 22% |
Researcher | 5 | 22% |
Student > Bachelor | 2 | 9% |
Unspecified | 1 | 4% |
Other | 0 | 0% |
Unknown | 4 | 17% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 3 | 13% |
Agricultural and Biological Sciences | 3 | 13% |
Medicine and Dentistry | 3 | 13% |
Chemistry | 3 | 13% |
Psychology | 1 | 4% |
Other | 2 | 9% |
Unknown | 8 | 35% |