4.5 Article

Proteomic alterations in extracellular vesicles induced by oncogenic PIK3CA mutations

期刊

PROTEOMICS
卷 22, 期 19-20, 页码 -

出版社

WILEY
DOI: 10.1002/pmic.202200077

关键词

exosomes; mass spectrometry; oncogenic mutation; PI3K; proteomics

资金

  1. TheWellcome Trust DBT India Alliance [IA/M/15/1/502023]

向作者/读者索取更多资源

This study investigated the impact of PIK3CA gene mutations on extracellular vesicles (EVs). Proteomic analysis of EVs revealed changes in protein composition associated with PIK3CA activating mutations, particularly in cell adhesion molecules and markers of tumor invasion and progression.
PIK3CA is one of the most frequently mutated genes in human cancers, with the two most prevalent activating mutations being E545K and H1047R. Although the altered intracellular signaling pathways in these cells have been described, the effect of these mutations on their extracellular vesicles (EVs) has not yet been reported. To study altered cellular physiology and intercellular communication through proteomic analysis of EVs, MCF10A cells and their isogenic mutant versions (PIK3CA E545K and H1047R) were cultured and their EVs enriched by differential ultracentrifugation. Proteins were extracted, digested with trypsin and the peptides labeled with tandem mass tag (TMT) reagents and analyzed by liquid chromatography tandem mass spectrometry (LC-MS/MS). Four thousand six hundred and fifty-five peptides were identified from 579 proteins of which 522 proteins have been previously described in EVs. Relative quantitation revealed altered levels of EV proteins including several cell adhesion molecules. Mesothelin, E-cadherin, and epithelial cell adhesion molecule were elevated in both mutant cell-derived EVs. Markers of tumor invasion and progression like galectin-3 and transforming growth factor beta induced protein were increased in both mutants. Overall, activating mutations in PIK3CA result in altered EV composition with characteristic changes associated with these hotspot mutations.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.5
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据