The Emerging Roles of Exosomes as EMT Regulators in Cancer

Abstract

Epithelial-mesenchymal transition (EMT) causes epithelial cells to lose their polarity and adhesion property, and endows them with migratory and invasive properties to enable them to become mesenchymal stem cells. EMT occurs throughout embryonic development, during wound healing, and in various pathological processes, including tumor progression. Considerable research in the last few decades has revealed that EMT is invariably related to tumor aggressiveness and metastasis. Apart from the interactions between numerous intracellular signaling pathways known to regulate EMT, extracellular modulators in the tumor microenvironment also influence tumor cells to undergo EMT, with extracellular vesicles (EVs) receiving increasing attention as EMT inducers. EVs comprise exosomes and microvesicles that carry proteins, nucleic acids, lipids, and other small molecules to stimulate EMT in cells. Among EVs, exosomes have been investigated in many studies, and their role has been found to be significant with respect to regulating intercellular communications. In this review, we summarize recent studies on exosomes and their cargoes that induce cancer-associated EMT. Furthermore, we describe the possible applications of exosomes as promising therapeutic strategies.

Keywords: Cancer; Epithelial mesenchymal transition; Exosome; Hippo pathway; Wnt/β-catenin pathway.

Figure 1

Schematic representation of exosomes. Exosomes are generated from multivesicular endosome (MVE), loaded with cellular components in donor cells, and secreted to the extracellular environment. Exosomes transfer proteins, nucleic acids, metabolites, and even organelles to recipient cells in both autocrinal and paracrinal manners. The uptake of exosomes is mediated by receptor activation, endocytosis, and membrane fusion.

Figure 2

Comprehensive schematic diagram of signaling pathways related to exosome-induced EMT in cancer. The principal signaling pathways and transcription factors involved in exosome-mediated EMT induction are depicted.

Figure 3

Schematic representation of exosome-induced EMT in cancer. The involvement of EMT-related signaling pathways during exosome-mediated EMT is depicted. The blue triangle indicates activation and red inverted triangle indicates inactivation of the signal.