Drug-resistant cancer cell-derived exosomal EphA2 promotes breast cancer metastasis via the EphA2-Ephrin A1 reverse signaling

• DOI: 10.1038/s41419-021-03692-x
• Publication Date: 2021-04-20T13:15:54Z
• Authors: Zicong Gao; Xingxing Han; Yuying Zhu; He Zhang; Ran Tian; Zhiyong Wang; Yanfen Cui; Zhaosong Wang; Ruifang Niu; Fei Zhang
• Keywords: EPH receptor A2; Exosome; Tumor progression

Abstract Tumor metastasis induced by drug resistance is a major challenge in successful cancer treatment. Nevertheless, the mechanisms underlying pro-invasive and metastatic ability of remain elusive. Exosome-mediated intercellular communications between cells stromal tumor microenvironment are required for initiation progression. Recent reports have shown that also promote aggression. However, little attention has been regarded on this aspect. Herein, we demonstrated drug-resistant cell-derived exosomes promoted invasion sensitive breast cells. Quantitative proteomic analysis showed EphA2 was rich from Exosomal conferred invasive/metastatic phenotype transfer to Moreover, exosomal activated ERK1/2 signaling through ligand Ephrin A1-dependent reverse pathway rather than forward pathway, thereby promoting Our findings indicate key functional role transmission aggressive do not rely direct cell–cell contact. study suggests increase may be an important mechanism chemotherapy/drug resistance-induced