文章基本信息

标题：Mechanistic Evaluation and Translational Signature of Gemcitabine-induced Chemoresistance by Quantitative Phosphoproteomics Analysis with iTRAQ Labeling Mass Spectrometry
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作者：Qingke Duan ; Hengqiang Zhao ; Zhengle Zhang 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2017
卷号：7
期号：1
DOI：10.1038/s41598-017-13330-2
语种：English
出版社：Springer Nature
摘要：One of the main causations of the poor prognosis of pancreatic cancer is the lack of effective chemotherapies. Gemcitabine is a widely used chemotherapeutic drug, but limited therapeutic efficacy is achieved due to chemoresistance. Recent studies demonstrated that the presence of cancer stem cells may lead to the failure of chemotherapy. Moreover, gemcitabine can promote the stemness of pancreatic cancer cells. We detected the alterations in protein phosphorylation and signaling pathways in pancreatic cancer cells after gemcitabine treatment using iTRAQ labeling LC-MS/MS, because it was featured with the advantages of strong separation ability and analysis range. A total of 232 differentially expressed phosphorylated proteins were identified in this study. Gene Ontology analysis revealed that nuclear lumen, nuclear part and organelle lumen were enriched for cell components and protein binding, poly (A) RNA binding and RNA binding were enriched for molecular function. A variety of signaling pathways were enriched based on KEGG analysis. AMPK, mTOR and PI3K/Akt pathways were verified after gemcitabine exposure. Moreover, we found there were complex interactions of phosphorylated proteins in modulating cancer stemness induced by gemcitabine exposure based on PPIs map. Our experiments may identify potential targets and strategies for sensitizing pancreatic cancer cells to gemcitabine.