The role of S6K1 in ER-positive breast cancer
The role of S6K1 in ER-positive breast cancer
复制标题
DOI：
10.4161/cc.21194
复制
发表时间：
2012-09-01
期刊：
影响因子：
4.3
通讯作者：
Holz, Marina K.
中科院分区：
文献类型：
--
作者：
Holz, Marina K.
40S核糖体S6激酶1(S6K1)是一种保守的丝氨酸/苏氨酸蛋白激酶，属于AGC蛋白激酶家族，该家族还包括Akt等多种蛋白。S6K1是哺乳动物雷帕霉素复合体1靶分子(MTORC1)下游的主要蛋白激酶效应器。S6K1对多种信号输入信号敏感，包括生长因子、氨基酸、能量水平和低氧。S6K1通过传递这些信号来调节越来越多的底物和相互作用的蛋白质，从而控制肿瘤发生过程，如细胞生长和增殖、细胞存活和凋亡以及细胞迁移和侵袭。一些证据表明，S6K1在雌激素受体(ER)阳性的乳腺癌中起着重要作用。S6K1直接磷酸化并激活ERα。此外，S6K1的表达受雌激素的调节。因此，mTORC1/S6K1信号通路的过度激活可能与乳腺癌ER阳性状态密切相关，可作为判断乳腺癌预后的指标和治疗的靶点。
The 40S ribosomal S6 kinase 1 (S6K1) is a conserved serine/threonine protein kinase that belongs to the AGC family of protein kinases, which also includes Akt and many others. S6K1 is the principal kinase effector downstream of the mammalian target of rapamycin complex 1 (mTORC1). S6K1 is sensitive to a wide range of signaling inputs, including growth factors, amino acids, energy levels and hypoxia. S6K1 relays these signals to regulate a growing list of substrates and interacting proteins in control of oncogenic processes, such as cell growth and proliferation, cell survival and apoptosis and cell migration and invasion. Several lines of evidence suggest an important role for S6K1 in estrogen receptor (ER)-positive breast cancer. S6K1 directly phosphorylates and activates ER alpha. Furthermore, S6K1 expression is estrogenically regulated. Therefore, hyperactivation of mTORC1/S6K1 signaling may be closely related to ER-positive status in breast cancer and may be utilized as a marker for prognosis and a therapeutic target.