mTOR/S6K1 和 MAPK/RSK 信号通路协同调节雌激素受体α丝氨酸 167 磷酸化。
mTOR/S6K1 and MAPK/RSK signaling pathways coordinately regulate estrogen receptor alpha serine 167 phosphorylation.
机构信息
Department of Biology, Stern College for Women of Yeshiva University, New York, NY 10016, USA.
出版信息
FEBS Lett. 2010 Jan 4;584(1):124-8. doi: 10.1016/j.febslet.2009.11.041.
Abstract
Resistance to anti-estrogen therapy is a major clinical concern in treatment of breast cancer. Estrogen-independent phosphorylation of estrogen receptor alpha, specifically on Ser167, is one of the contributing causes to development of resistance, and a prognostic marker for the disease. Here, we dissect the signaling pathways responsible for Ser167 phosphorylation. We report that the mTOR/S6K1 and MAPK/RSK contribute non-overlapping inputs into ERalpha activation via Ser167 phosphorylation. This cooperation may be targeted in breast cancer treatment by a combination of mTOR and MAPK inhibitors.
摘要
抗雌激素治疗耐药是乳腺癌治疗中的一个主要临床关注点。雌激素受体α的雌激素非依赖性磷酸化，特别是丝氨酸 167 的磷酸化，是导致耐药性发展的原因之一，也是该疾病的预后标志物。在这里，我们剖析了导致丝氨酸 167 磷酸化的信号通路。我们报告称，mTOR/S6K1 和 MAPK/RSK 通过丝氨酸 167 磷酸化，为 ERalpha 的激活提供非重叠的输入。通过联合使用 mTOR 和 MAPK 抑制剂，这种合作可能成为乳腺癌治疗的靶点。
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