Exosome biogenesis – machinery, regulation, and therapeutic implications in cancer

Exosomes are well-known key mediators of intercellular communication and contribute to various physiological and pathological processes. Their biogenesis involves four key steps, including cargo sorting, MVB formation and maturation, transport of MVBs, and MVB fusion with the plasma membrane. Each process is modulated through the competition or coordination of multiple mechanisms, whereby diverse repertoires of molecular cargos are sorted into distinct subpopulations of exosomes, resulting in the high heterogeneity of exosomes. Intriguingly, cancer cells exploit various strategies, such as aberrant gene expression, posttranslational modifications, and altered signaling pathways, to regulate the biogenesis, composition, and eventually functions of exosomes to promote cancer progression. Therefore, exosome biogenesis-targeted therapy is being actively explored. Researchers from Zhengzhou University systematically summarize recent progress in understanding the machinery of exosome biogenesis and how it is regulated in the context of cancer. In particular, they highlight pharmacological targeting of exosome biogenesis as a promising cancer therapeutic strategy.

Overview of the process for exosome biogenesis

Fig. 1

MVBs take the center of exosome biogenesis. Generally, MVBs are derived from endocytosis, during which different mechanisms mediate the inward budding of the plasma membrane and the formation of early endosomes. MVBs can dynamically communicate with other organelles or compartments including trans-Golgi network (TGN), endoplasmic reticulum (ER), mitochondrion, phagosome, RNA granule and micronuclei, et al. Therefore, different repertoires of cargos such as proteins, RNAs, DNAs or lipids are sorted into MVBs. After the maturation of MVBs, they can either fuse with lysosome to be degraded or fuse with plasma membrane to release ILVs, the so-called exosomes. Of note, MVB can fuse with autophagosome to form amphisome, which can either fuse with lysosome to be degraded or fuse with plasma membrane to secret exosomes

Han QF, Li WJ, Hu KS, Gao J, Zhai WL, Yang JH, Zhang SJ. (2022) Exosome biogenesis: machinery, regulation, and therapeutic implications in cancer. Mol Cancer 21(1):207. [article]

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