Exosomes participate in cancer progression and metastasis by transferring bioactive molecules between cancer and various cells in the local and distant microenvironments. Such intercellular cross‐talk results in changes in multiple cellular and biological functions in recipient cells. Several hallmarks of cancer have reportedly been impacted by this exosome‐mediated cell‐to‐cell communication, including modulating immune responses, reprogramming stromal cells, remodeling the architecture of the extracellular matrix, or even endowing cancer cells with characteristics of drug resistance. Selectively, loading specific oncogenic molecules into exosomes highlights exosomes as potential diagnostic biomarkers as well as therapeutic targets. In addition, exosome‐based drug delivery strategies in preclinical and clinical trials have been shown to dramatically decrease cancer development. In the present review, we summarize the significant aspects of exosomes in cancer development that can provide novel strategies for potential clinical applications.
Growth factor receptor bound protein-7 (Grb7) is a multi-domain adaptor protein that is co-opted by numerous tyrosine kinases involved in various cellular signaling and functions. The molecular mechanisms underlying the regulation of Grb7 remain unclear. Here, we revealed a novel negative post-translational regulation of Grb7 by the peptidyl-prolyl cis/trans isomerase, Pin1. Our data show that phosphorylation of Grb7 protein on the Ser194-Pro motif by c-Jun N-terminal kinase facilitates its binding with the WW domain of Pin1. Subsequently, Grb7 is degraded by the ubiquitin- and proteasome-dependent proteolytic pathway. Indeed, we found that Pin1 exerts its peptidyl-prolyl cis/trans isomerase activity in the modulation of Grb7 protein stability in regulation of cell cycle progression at the G2-M phase. This study illustrates a novel regulatory mechanism in modulating Grb7-mediated signaling, which may take part in pathophysiological consequences.
In mammalian cells, extracellular vesicles (EVs) derived from the endosomal system carry many different kinds of bioactive molecule to deliver to recipient cells in a paracrine or endocrine manner. EVs can mediate local and systemic intercellular communications, including reeducating stromal cells, remodeling the architecture of the tumor microenvironment, modulating cancer metabolism and metastases, or even conferring drug resistance. Because the molecular and functional characteristics of prostate cancer (PCa) evolve over time, the bioactive molecule profiles/signatures of tumor-derived EVs (TDEs) reflect the real-time status of cancer cells. TDEs appear to be valuable diagnostic and prognostic biomarkers as well as potential therapeutic vehicles, suggesting their essential role in precision medicine of disease management. We summarized critical aspects of TDEs in PCa and discussed their potential clinical applications.
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