Role of protein kinase D signaling in pancreatic cancer.
Role of protein kinase D signaling in pancreatic cancer.
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蛋白激酶 D 信号传导在胰腺癌中的作用。
DOI：
10.1016/j.bcp.2010.07.002
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发表时间：
2010-12-15
影响因子：
5.8
通讯作者：
Rozengurt, Enrique
中科院分区：
文献类型：
--
作者：
Guha, Sushovan;Tanasanvimon, Suebpong;Sinnett-Smith, James;Rozengurt, Enrique
胰腺导管腺癌（PDAC）是最致命的癌症之一，生存率低。它对常规治疗的顽固性使PDAC成为具有早期转移潜力的侵袭性疾病。因此，迫切需要PDAC治疗的新靶点。PDAC的进展涉及多种信号转导途径。这些途径刺激其靶细胞中细胞内信使的产生以改变其行为，包括脂质衍生的二酰基甘油（DAG）。DAG的主要细胞内靶点之一是蛋白激酶C（PKC）家族。然而，PKC介导的信号被细胞解码的机制仍然不完全清楚。蛋白激酶D1（PKD或PKD1，最初称为非典型PKCμ）是一种新的蛋白激酶家族的创始成员，该家族包括两种与PKD具有广泛整体同源性的额外蛋白激酶，称为PKD2和PKD3。PKD家族在DAG和PKC启动的信号转导通路中占有独特的地位。PKD位于PKCs的下游，是一种新的信号转导途径，参与多种基本生物学过程的调节。我们和其他人已经表明PKD介导的信号通路促进PDAC中的有丝分裂和血管生成。我们最近的观察表明，PKD也增强PDAC细胞的耐药性和侵袭潜力。本文将简要介绍PKD家族在包括PDAC在内的多种肿瘤中的生物学作用。此外，这篇综述将强调我们的最新进展与发展的一个强大的PKD家族抑制剂和它的效果在体外和体内PDAC。
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers with dismal survival rates. Its intransigence to conventional therapy renders PDAC an aggressive disease with early metastatic potential. Thus, novel targets for PDAC therapy are urgently needed. Multiple signal transduction pathways are implicated in progression of PDAC. These pathways stimulate production of intracellular messengers in their target cells to modify their behavior, including the lipid-derived diacylglycerol (DAG). One of the prominent intracellular targets of DAG is the protein kinase C (PKC) family. However, the mechanisms by which PKC-mediated signals are decoded by the cell remain incompletely understood. Protein kinase D1 (PKD or PKD1, initially called atypical PKCµ), is the founding member of a novel protein kinase family that includes two additional protein kinases that share extensive overall homology with PKD, termed PKD2, and PKD3. The PKD family occupies a unique position in the signal transduction pathways initiated by DAG and PKC. PKD lies downstream of PKCs in a novel signal transduction pathway implicated in the regulation of multiple fundamental biological processes. We and others have shown that PKD-mediated signaling pathways promote mitogenesis and angiogenesis in PDAC. Our recent observations demonstrate that PKD also potentiates chemoresistance and invasive potential of PDAC cells. This review will briefly highlight diverse biological roles of PKD family in multiple neoplasias including PDAC. Further, this review will underscore our latest advancement with the development of a potent PKD family inhibitor and its effect both in vitro and in vivo in PDAC.
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影响因子：
21.3
作者：
Eiseler T;Döppler H;Yan IK;Kitatani K;Mizuno K;Storz P
通讯作者：
Storz P
DOI：
10.1523/jneurosci.1879-08.2008
发表时间：
2008-09-10
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Bisbal M;Conde C;Donoso M;Bollati F;Sesma J;Quiroga S;Díaz Añel A;Malhotra V;Marzolo MP;Cáceres A
通讯作者：
Cáceres A
影响因子：
3.8
作者：
Denham, DW;Franz, MG;Norman, J
通讯作者：
Norman, J
DOI：
10.1006/bbrc.2000.2335
发表时间：
2000-03-24
影响因子：
3.1
作者：
Ehlers, RA;Zhang, YJ;Evers, BM
通讯作者：
Evers, BM
影响因子：
64.8
作者：
Chang, LF;Karin, M
通讯作者：
Karin, M