Functional Linkage of RKIP to the Epithelial to Mesenchymal Transition and Autophagy during the Development of Prostate Cancer.
Functional Linkage of RKIP to the Epithelial to Mesenchymal Transition and Autophagy during the Development of Prostate Cancer.
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DOI：
10.3390/cancers10080273
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发表时间：
2018-08-16
期刊：
影响因子：
5.2
通讯作者：
Kim DR
中科院分区：
文献类型：
--
作者：
Ahmed M;Lai TH;Zada S;Hwang JS;Pham TM;Yun M;Kim DR
Raf 激酶抑制剂蛋白 (RKIP) 作为多功能衔接蛋白在许多信号通路中发挥着关键作用。特别是，某些类型的癌细胞中 RKIP 功能的丧失会导致上皮间质转化（EMT）并促进癌症转移。此外，RKIP 通过调节 LC3 脂化和 mTORC1 来抑制自噬。 RKIP 依赖性自噬抑制与 EMT 和癌症进展之间的关系仍在研究中。在这项研究中，我们研究了 RKIP 在前列腺癌进展过程中与 EMT 和自噬中关键基因产物相互作用的方式。我们首先使用相应的基因本体术语来识别感兴趣的基因产物。将加权基因共表达网络分析（WGCNA）应用于三组前列腺组织的基因表达数据集；良性前列腺增生、原发性和转移性癌症。我们发现了两个高度共表达基因的模块，它们保存在前列腺癌组织的其他独立数据集中。 RKIP 显示出与一种 EMT 和七种自噬基因产物（TGFBR1、PIK3C3、PIK3CB、TBC1D25、TBC1D5、TOLLIP、WDR45 和 WIPI1）的潜在新相互作用。此外，我们还鉴定了几种可以调节这些基因产物表达的上游转录调节剂。最后，我们通过在前列腺癌细胞系中使用共聚焦显微镜分析进行共定位来验证一些 RKIP 新颖的相互作用。总而言之，RKIP 与 EMT 和自噬相互作用，作为发展前列腺癌的同一功能单元的一部分。
Raf kinase inhibitor protein (RKIP) plays a critical role in many signaling pathways as a multi-functional adapter protein. In particular, the loss of RKIP’s function in certain types of cancer cells results in epithelial to mesenchymal transition (EMT) and the promotion of cancer metastasis. In addition, RKIP inhibits autophagy by modulating LC3-lipidation and mTORC1. How the RKIP-dependent inhibition of autophagy is linked to EMT and cancer progression is still under investigation. In this study, we investigated the ways by which RKIP interacts with key gene products in EMT and autophagy during the progression of prostate cancer. We first identified the gene products of interest using the corresponding gene ontology terms. The weighted-gene co-expression network analysis (WGCNA) was applied on a gene expression dataset from three groups of prostate tissues; benign prostate hyperplasia, primary and metastatic cancer. We found two modules of highly co-expressed genes, which were preserved in other independent datasets of prostate cancer tissues. RKIP showed potentially novel interactions with one EMT and seven autophagy gene products (TGFBR1; PIK3C3, PIK3CB, TBC1D25, TBC1D5, TOLLIP, WDR45 and WIPI1). In addition, we identified several upstream transcription modulators that could regulate the expression of these gene products. Finally, we verified some RKIP novel interactions by co-localization using the confocal microscopy analysis in a prostate cancer cell line. To summarize, RKIP interacts with EMT and autophagy as part of the same functional unit in developing prostate cancer.
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影响因子：
48
作者：
Huber W;Carey VJ;Gentleman R;Anders S;Carlson M;Carvalho BS;Bravo HC;Davis S;Gatto L;Girke T;Gottardo R;Hahne F;Hansen KD;Irizarry RA;Lawrence M;Love MI;MacDonald J;Obenchain V;Oleś AK;Pagès H;Reyes A;Shannon P;Smyth GK;Tenenbaum D;Waldron L;Morgan M
通讯作者：
Morgan M
WGCNA：用于加权相关网络分析的 R 包。
影响因子：
3
作者：
Langfelder P;Horvath S
通讯作者：
Horvath S
影响因子：
11.2
作者：
Khalil BD;Hsueh C;Cao Y;Abi Saab WF;Wang Y;Condeelis JS;Bresnick AR;Backer JM
通讯作者：
Backer JM
影响因子：
64.5
作者：
Cancer Genome Atlas Research Network
通讯作者：
Cancer Genome Atlas Research Network
影响因子：
4.3
作者：
Langfelder P;Luo R;Oldham MC;Horvath S
通讯作者：
Horvath S