小柯机器人

在小细胞肺癌干细胞中，无偏倚的蛋白质组学分析揭示了可靶向的GNAS / PKA / PP2A轴，这一成果由美国斯坦福大学Julien Sage团队取得。2020年6月11日，《癌细胞》在线发表了这一成果。

使用无偏倚的激酶分析，研究人员确定蛋白激酶A（PKA）是小细胞肺癌（SCLC）中的活性激酶。利用遗传方法激活PP2A磷酸酶或药物抑制PKA活性可抑制SCLC在培养基和体内的扩增。 相反，PKA激活剂GNAS（G蛋白α亚基）在一小部分人类SCLC中被激活并促进SCLC的发展。

磷酸蛋白质组学分析确定了许多PKA的底物和其作用机理。 特别是在移植研究中，PKA活性是SCLC干细胞繁殖所必需的。顽固性癌症的广泛蛋白质组学分析可能发现新的、可靶向的信号网络，例如SCLC中的GNAS / PKA / PP2A轴。

附：英文原文

Title: Unbiased Proteomic Profiling Uncovers a Targetable GNAS/PKA/PP2A Axis in Small Cell Lung Cancer Stem Cells

Author: Garry L. Coles, Sandra Cristea, James T. Webber, Rebecca S. Levin, Steven M. Moss, Andy He, Jaya Sangodkar, Yeonjoo C. Hwang, Julia Arand, Alexandros P. Drainas, Nancie A. Mooney, Janos Demeter, Jessica N. Spradlin, Brandon Mauch, Vicky Le, Yan Ting Shue, Julie H. Ko, Myung Chang Lee, Christina Kong, Daniel K. Nomura, Michael Ohlmeyer, Danielle L. Swaney, Nevan J. Krogan, Peter K. Jackson, Goutham Narla, John D. Gordan, Kevan M. Shokat, Julien Sage

Issue&Volume: 2020-06-11

Abstract: Using unbiased kinase profiling, we identified protein kinase A (PKA) as an activekinase in small cell lung cancer (SCLC). Inhibition of PKA activity genetically, orpharmacologically by activation of the PP2A phosphatase, suppresses SCLC expansionin culture and in vivo. Conversely, GNAS (G-protein α subunit), a PKA activator that is genetically activatedin a small subset of human SCLC, promotes SCLC development. Phosphoproteomic analysesidentified many PKA substrates and mechanisms of action. In particular, PKA activityis required for the propagation of SCLC stem cells in transplantation studies. Broadproteomic analysis of recalcitrant cancers has the potential to uncover targetablesignaling networks, such as the GNAS/PKA/PP2A axis in SCLC.

DOI: 10.1016/j.ccell.2020.05.003

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(20)30253-1

Cancer Cell：《癌细胞》，创刊于2002年。隶属于细胞出版社，最新IF：38.585
官方网址：https://www.cell.com/cancer-cell/home
投稿链接：https://www.editorialmanager.com/cancer-cell/default.aspx