Proteomic and Phosphoproteomic Profiling Reveals the Oncogenic Role of Protein Kinase D Family Kinases in Cholangiocarcinoma.
Proteomic and Phosphoproteomic Profiling Reveals the Oncogenic Role of Protein Kinase D Family Kinases in Cholangiocarcinoma.
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蛋白质组学和磷酸化蛋白质组学分析揭示了蛋白激酶 D 家族激酶在胆管癌中的致癌作用
DOI：
10.3390/cells11193088
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发表时间：
2022-09-30
期刊：
影响因子：
6
通讯作者：
Wang, Jianming
中科院分区：
文献类型：
--
作者：
Lu, Yun;Li, Xiangyu;Zhao, Kai;Shi, Yuanxin;Deng, Zhengdong;Yao, Wei;Wang, Jianming
胆管癌（Cholangiocarcinoma，CCA）是一种以蛋白质表达和磷酸化信号异常为特征的恶性肿瘤。然而，CCA的蛋白质和磷酸化特征却鲜为人知。在这里，我们对CCA患者的肿瘤和正常邻近组织（NAT）进行了蛋白质组学和磷酸化蛋白质组学分析，并预测了11个与CCA高度相关的PK，并对功能性蛋白激酶（PK）（CifPK）管道进行了全面的推断。除了两个已知的CCA相关的PKs，我们筛选了其余的候选人，并发现了五个PKs作为新的监管机构在CCA。具体而言，蛋白激酶D（PKD）家族成员，包括PRKD 1，PRKD 2和PRKD 3，被确定为CCA的关键调节因子。此外，PKD家族的泛抑制剂1-naphthyl PP 1（1-NA-PP 1）被验证为抑制CCA细胞的增殖、迁移和侵袭能力的有效药剂。这项研究揭示了与CCA相关的新PK，并建议PRKD激酶作为CCA的新治疗靶点。
Cholangiocarcinoma (CCA) is a lethal malignancy in the hepatobiliary system, with dysregulated protein expression and phosphorylation signaling. However, the protein and phosphorylation signatures of CCAs are little-known. Here, we performed the proteomic and phosphoproteomic profiling of tumors and normal adjacent tissues (NATs) from patients with CCA and predicted eleven PKs high-potentially related to CCA with a comprehensive inference of the functional protein kinases (PKs) (CifPK) pipeline. Besides the two known CCA-associated PKs, we screened the remaining candidates and uncovered five PKs as novel regulators in CCA. Specifically, the protein kinase D (PKD) family members, including PRKD1, PRKD2, and PRKD3, were identified as critical regulators in CCA. Moreover, the pan-inhibitor of the PKD family, 1-naphthyl PP1 (1-NA-PP1), was validated as a potent agent for inhibiting the proliferation, migration, and invasion ability of CCA cells. This study reveals new PKs associated with CCA and suggests PRKD kinases as novel treatment targets for CCA.
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影响因子：
3.3
作者：
Kannaiyan R;Mahadevan D
通讯作者：
Mahadevan D
DOI：
10.1038/s41572-021-00300-2
发表时间：
2021-09-09
期刊：
Nature reviews. Disease primers
影响因子：
--
作者：
通讯作者：
--
CX-4945通过与CK2无关的机制在胆管癌细胞系中诱导甲基症。
影响因子：
5.2
作者：
Lertsuwan J;Lertsuwan K;Sawasdichai A;Tasnawijitwong N;Lee KY;Kitchen P;Afford S;Gaston K;Jayaraman PS;Satayavivad J
通讯作者：
Satayavivad J
DOI：
10.1056/nejmoa1502309
发表时间：
2015-08-20
期刊：
The New England journal of medicine
影响因子：
--
作者：
Hyman DM;Puzanov I;Subbiah V;Faris JE;Chau I;Blay JY;Wolf J;Raje NS;Diamond EL;Hollebecque A;Gervais R;Elez-Fernandez ME;Italiano A;Hofheinz RD;Hidalgo M;Chan E;Schuler M;Lasserre SF;Makrutzki M;Sirzen F;Veronese ML;Tabernero J;Baselga J
通讯作者：
Baselga J
影响因子：
5.5
作者：
Deng Z;Li X;Shi Y;Lu Y;Yao W;Wang J
通讯作者：
Wang J