EWI‐2 controls nucleocytoplasmic shuttling of EGFR signaling molecules and miRNA sorting in exosomes to inhibit prostate cancer cell metastasis. Issue 5 (27th March 2021)

• Record Type: Journal Article
• Authors: Fu, Chenying; Zhang, Qing; Wang, Ani; Yang, Songpeng; Jiang, Yangfu; Bai, Lin; Wei, Quan
• Is Part Of: Molecular oncology. Volume 15:Issue 5(2021)
• Page Start: 1543
• Page End: 1565
• Publication Date: 2021-03-27
• Subjects: cancer metastasis -- EGF receptor -- EWI‐2/PGRL -- exosomes -- miR‐3934‐5p -- nuclear translocation; Cancer -- Molecular aspects -- Periodicals; 616.994005
• DOI: 10.1002/1878-0261.12930
• Languages: English
• ISSNs: 1574-7891

Abstract

Abstract : Early and accurate diagnosis of prostate cancer (PCa) is extremely important, as metastatic PCa remains hard to treat. EWI‐2, a member of the Ig protein subfamily, is known to inhibit PCa cell migration. In this study, we found that EWI‐2 localized on both the cell membrane and exosomes regulates the distribution of miR‐3934‐5p between cells and exosomes. Interestingly, we observed that EWI‐2 is localized not only on the plasma membrane but also on the nuclear envelope (nuclear membrane), where it regulates the nuclear translocation of signaling molecules and miRNA. Collectively, these functions of EWI‐2 found in lipid bilayers appear to regulate PCa cell metastasis through the epidermal growth factor receptor‐mitogen‐activated protein kinase‐extracellular‐signal‐regulated kinase (EGFR‐MAPK‐ERK) pathway. Our research provides new insights into the molecular function of EWI‐2 on PCa metastasis, and highlights EWI‐2 as a potential PCa biomarker. Abstract : Our findings identify EWI‐2 as a potential prostate cancer (PCa) biomarker. EWI‐2 is involved in PCa metastasis through its localization on lipid bilayers where it facilitates nucleocytoplasmic shuttling of EGFR signaling molecules and also regulates microRNA sorting in exosomes. These molecular functions of EWI‐2 result in downstream activation of the epidermal growth factor receptor‐mitogen‐activated protein kinase‐extracellular‐signal‐regulated kinase (EGFR‐MAPK‐ERK) signaling pathway and promote PCa cell migration.