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

Qingfang HanDepartment of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, ChinaWenjia LiGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation Medical Research Center, Sun Yat-Sen Memorial Hospital Sun Yat-Sen University, Guangzhou, 510120, ChinaKaishun HuGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation Medical Research Center, Sun Yat-Sen Memorial Hospital Sun Yat-Sen University, Guangzhou, 510120, ChinaJie GaoHenan Diagnosis & Treatment League for Hepatopathy, Zhengzhou, 450052, Henan, ChinaWenlong ZhaiDepartment of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China. [email protected]Jinghua YangClinical Systems Biology Key Laboratories of Henan, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China. [email protected]Shuijun ZhangDepartment of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China. [email protected]
2022en
ABI

Аннотация

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. In this review, we systematically summarize recent progress in understanding the machinery of exosome biogenesis and how it is regulated in the context of cancer. In particular, we highlight pharmacological targeting of exosome biogenesis as a promising cancer therapeutic strategy.

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