Fig. 1

A schematic representation for the biological process of exosomes and key steps affected by hypoxia. ①Hypoxia affects cargo synthesis at translation level. ②Hypoxia influence exosome release and cargo-sorting by cargo-loading key tools (such as YBX1 and hnRNPA1). ③Hypoxia blocks MVBs degradation to increase exosome release (such as downregulating Rab7). ④Hypoxia causes overexpression of key molecules involving in MVBs transport towards plasma membrane to increase exosome release (such as Rab27). ⑤Hypoxia may increase exosome release by promoting the fusion between MVBs and plasma membrane (such as SNARE protein). ⑥Intercellular transport includes long-distance transport to distant recipient cells by circulation system (left) short-distance transport in local TME (right). Smaller exosome size induced by hypoxia seems to facilitate circulation transport, but it is not been proved. Acidic microenvironment, a result of hypoxia, may be beneficial to transport under local acidic microenvironment. ⑦Hypoxia and low-pH can increase exosome uptake efficiency. It has been proved that membrane composition changed by low-pH influence exosome uptake by homologous cells, but it was not explored under hypoxia. It remains unknown that which of exosome uptake methods is more obviously changed by hypoxia