Oncogenic Protein Kinase D3 Regulating Networks in Invasive Breast Cancer.
Oncogenic Protein Kinase D3 Regulating Networks in Invasive Breast Cancer.
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DOI：
10.7150/ijbs.18472
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发表时间：
2017
影响因子：
9.2
通讯作者：
Chen L
中科院分区：
文献类型：
--
作者：
Liu Y;Li J;Zhang J;Yu Z;Yu S;Wu L;Wang Y;Gong X;Wu C;Cai X;Mo L;Wang M;Gu J;Chen L
蛋白激酶D3（PRKD 3）在浸润性乳腺癌中作为重要的致癌驱动因子发挥作用，浸润性乳腺癌是女性死亡的主要原因。然而，PRKD 3调节网络在很大程度上是未知的。本研究通过对磷酸化蛋白质组、相互作用组和转录组的研究，系统地探讨PRKD 3的调控网络，以期揭示PRKD 3在浸润性乳腺癌中的分子机制。使用iTRAQ，从4619个磷酸位点中鉴定出270种蛋白质为PRKD 3调节的磷蛋白，其匹配来自2016种磷蛋白的3666种磷酸肽，p值<0.005。使用亲和素微阵列的转录组分析鉴定了45个PRKD 3调节基因，其中在沉默PRKD 3后，20个基因上调，25个基因下调，p值<0.005。利用Co-IP结合MS鉴定，从2659个多肽中鉴定出606个与PRKD 3相互作用的蛋白。对PRKD 3调节的磷蛋白、相互作用蛋白和调节基因的进一步网络分析揭示了19个枢纽节点，包括ELAVL 1、UBC和BRCA 1。UBC被认为是PRKD 3调节网络中最常见的枢纽节点。富集的通路分析表明，PRKD 3调节有助于多种癌症相关事件的通路，包括细胞周期，迁移等。细胞周期和细胞迁移相关途径在PRKD 3网络中的富集解释了致癌PRKD 3的缺失导致细胞周期改变和细胞迁移能力降低的观察结果。综上所述，我们目前的研究提供了有价值的信息PRKD 3在浸润性乳腺癌中的作用以及分子机制。
Protein Kinase D3 (PRKD3) functions as an important oncogenic driver in invasive breast cancer, which is the leading cause of women mortality. However, PRKD3 regulating network is largely unknown. In this study, we systematically explored PRKD3 regulating networks via investigating phosphoproteome, interactome and transcriptome to uncover the molecular mechanism of PRKD3 in invasive breast cancer. Using iTRAQ, 270 proteins were identified as PRKD3 regulated phosphoproteins from 4619 phosphosites matching 3666 phosphopeptides from 2016 phosphoproteins with p-value <0.005. Transcriptome analysis using affymetrix microarray identified 45 PRKD3 regulated genes, in which 20 genes were upregulated and 25 genes were downregulated with p-value <0.005 upon silencing PRKD3. Using Co-IP in combination of MS identification, 606 proteins were identified to be PRKD3 interacting proteins from 2659 peptides. Further network analysis of PRKD3 regulated phosphoproteins, interacting proteins and regulated genes, reveals 19 hub nodes, including ELAVL1, UBC and BRCA1. UBC was recognized as the most common hub node in PRKD3 regulating networks. The enriched pathway analysis reveals that PRKD3 regulates pathways contributing to multiple cancer related events, including cell cycle, migration and others. Enrichment of cell cycle and cell mobility related pathways across PRKD3 networks, explained the observations that depletion of oncogenic PRKD3 led to alternation of cell cycle and decrease of cell migration ability. Taken together, our current study provided valuable information on the roles as well as the molecular mechanisms of PRKD3 in invasive breast cancer.