Survey of tyrosine kinase signaling reveals ROS kinase fusions in human cholangiocarcinoma.
Survey of tyrosine kinase signaling reveals ROS kinase fusions in human cholangiocarcinoma.
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DOI：
10.1371/journal.pone.0015640
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发表时间：
2011-01-06
期刊：
影响因子：
3.7
通讯作者：
Comb MJ
中科院分区：
文献类型：
--
作者：
Gu TL;Deng X;Huang F;Tucker M;Crosby K;Rimkunas V;Wang Y;Deng G;Zhu L;Tan Z;Hu Y;Wu C;Nardone J;MacNeill J;Ren J;Reeves C;Innocenti G;Norris B;Yuan J;Yu J;Haack H;Shen B;Peng C;Li H;Zhou X;Liu X;Rush J;Comb MJ
胆管癌，又称胆管癌，是第二常见的原发性肝癌，中位生存期不到2年。这种疾病发生的分子机制尚不清楚。为了研究胆管癌中激活的酪氨酸激酶信号，我们采用免疫亲和谱联用质谱技术，鉴定了原发性胆管癌患者中DDR1、EPHA2、EGFR和ROS酪氨酸激酶，以及来自750种不同蛋白质的1000多个酪氨酸磷酸化位点。此外，我们证实8.7%（23名患者中的2名）胆管癌患者存在ROS激酶融合。在3T3细胞中表达ROS融合体具有体内和体外转化能力，并对其激酶抑制剂有反应。我们的数据表明，ROS激酶是胆管癌治疗靶点和诊断分子标记物的有希望的候选物。胆管癌中ROS酪氨酸激酶融合的鉴定，以及肺癌和胶质母细胞瘤中其他ROS激酶融合的存在，表明有必要对癌症中活化的ROS激酶进行更广泛的筛选。
Cholangiocarcinoma, also known as bile duct cancer, is the second most common primary hepatic carcinoma with a median survival of less than 2 years. The molecular mechanisms underlying the development of this disease are not clear. To survey activated tyrosine kinases signaling in cholangiocarcinoma, we employed immunoaffinity profiling coupled to mass spectrometry and identified DDR1, EPHA2, EGFR, and ROS tyrosine kinases, along with over 1,000 tyrosine phosphorylation sites from about 750 different proteins in primary cholangiocarcinoma patients. Furthermore, we confirmed the presence of ROS kinase fusions in 8.7% (2 out of 23) of cholangiocarcinoma patients. Expression of the ROS fusions in 3T3 cells confers transforming ability both in vitro and in vivo, and is responsive to its kinase inhibitor. Our data demonstrate that ROS kinase is a promising candidate for a therapeutic target and for a diagnostic molecular marker in cholangiocarcinoma. The identification of ROS tyrosine kinase fusions in cholangiocarcinoma, along with the presence of other ROS kinase fusions in lung cancer and glioblastoma, suggests that a more broadly based screen for activated ROS kinase in cancer is warranted.
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影响因子：
3.4
作者：
Deutsch, Eric W.;Mendoza, Luis;Shteynberg, David;Farrah, Terry;Lam, Henry;Tasman, Natalie;Sun, Zhi;Nilsson, Erik;Pratt, Brian;Prazen, Bryan;Eng, Jimmy K.;Martin, Daniel B.;Nesvizhskii, Alexey I.;Aebersold, Ruedi
通讯作者：
Aebersold, Ruedi
DOI：
10.1038/nrc1299
发表时间：
2004-03
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
通讯作者：
--
影响因子：
46.9
作者：
Rush, J;Moritz, A;Comb, MJ
通讯作者：
Comb, MJ
影响因子：
11.2
作者：
Charest, Al;Wilker, Erik W.;Housman, David
通讯作者：
Housman, David
影响因子：
25.7
作者：
Seki, Ekihiro;Kondo, Yuichi;Nakanishi, Kenji
通讯作者：
Nakanishi, Kenji