PMID- 35954442 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220815 IS - 2072-6694 (Print) IS - 2072-6694 (Electronic) IS - 2072-6694 (Linking) VI - 14 IP - 15 DP - 2022 Aug 3 TI - Exosomes from EGFR-Mutated Adenocarcinoma Induce a Hybrid EMT and MMP9-Dependant Tumor Invasion. LID - 10.3390/cancers14153776 [doi] LID - 3776 AB - Exosomes, a class of extra cellular nano-sized vesicles (EVs), and their contents have gained attention as potential sources of information on tumor detection and regulatory drivers of tumor progression and metastasis. The effect of exosomes isolated from patients with an Epidermal Growth Factor Receptor (EGFR)-mutated adenocarcinoma on the promotion of epithelial-mesenchymal transition (EMT) and invasion were examined. Exosomes derived from serum of patients with EGFR-mutated non-small cell lung cancer (NSCLC) mediate the activation of the Phosphoinositide 3-kinase (PI3K)/AKT/ mammalian target of rapamycin (mTOR) pathway and induce an invasion through the up-regulation of matrix metalloproteinase-9 (MMP-9) in A549 cells. We observed a significant increase in the expression of vimentin, a mesenchymal marker, while retaining the epithelial characteristics, as evidenced by the unaltered levels of E-cadherin and Epithelial cell adhesion molecule (EPCAM). We also observed an increase of nuclear factor erythroid 2-related factor 2 (NFR2) and P-cadherin expression, markers of hybrid EMT. Exosomes derived from EGFR-mutated adenocarcinoma serum could be a potential mediator of hybrid EMT and tumor invasion. Understanding how cancerous cells communicate and interact with their environment via exosomes will improve our understanding of lung cancer progression and metastasis formation. FAU - Jouida, Amina AU - Jouida A AUID- ORCID: 0000-0002-0042-5784 AD - School of Medicine, University College Dublin, D14 E099 Dublin, Ireland. FAU - O'Callaghan, Marissa AU - O'Callaghan M AD - School of Medicine, University College Dublin, D14 E099 Dublin, Ireland. AD - Department of Respiratory Medicine, St. Vincent's University Hospital, D04 T6F4 Dublin, Ireland. FAU - Mc Carthy, Cormac AU - Mc Carthy C AUID- ORCID: 0000-0003-2896-5210 AD - School of Medicine, University College Dublin, D14 E099 Dublin, Ireland. AD - Department of Respiratory Medicine, St. Vincent's University Hospital, D04 T6F4 Dublin, Ireland. FAU - Fabre, Aurelie AU - Fabre A AD - School of Medicine, University College Dublin, D14 E099 Dublin, Ireland. AD - Department of Respiratory Medicine, St. Vincent's University Hospital, D04 T6F4 Dublin, Ireland. FAU - Nadarajan, Parthiban AU - Nadarajan P AD - School of Medicine, University College Dublin, D14 E099 Dublin, Ireland. AD - Department of Respiratory Medicine, St. Vincent's University Hospital, D04 T6F4 Dublin, Ireland. FAU - Keane, Michael P AU - Keane MP AUID- ORCID: 0000-0003-4507-0742 AD - School of Medicine, University College Dublin, D14 E099 Dublin, Ireland. AD - Department of Respiratory Medicine, St. Vincent's University Hospital, D04 T6F4 Dublin, Ireland. LA - eng PT - Journal Article DEP - 20220803 PL - Switzerland TA - Cancers (Basel) JT - Cancers JID - 101526829 PMC - PMC9367273 OTO - NOTNLM OT - EGFR OT - exosome OT - lung cancer OT - partial EMT COIS- The authors declare no conflict of interest. EDAT- 2022/08/13 06:00 MHDA- 2022/08/13 06:01 PMCR- 2022/08/03 CRDT- 2022/08/12 01:05 PHST- 2022/06/28 00:00 [received] PHST- 2022/07/23 00:00 [revised] PHST- 2022/07/26 00:00 [accepted] PHST- 2022/08/12 01:05 [entrez] PHST- 2022/08/13 06:00 [pubmed] PHST- 2022/08/13 06:01 [medline] PHST- 2022/08/03 00:00 [pmc-release] AID - cancers14153776 [pii] AID - cancers-14-03776 [pii] AID - 10.3390/cancers14153776 [doi] PST - epublish SO - Cancers (Basel). 2022 Aug 3;14(15):3776. doi: 10.3390/cancers14153776.