The mechanism by which ADAM10 cleaves Notch2 and upregulates RAB5 to regulate exosome secretion in pancreatic cancer

Abstract

Abstract Background At present, the clinical diagnosis and treatment of pancreatic cancer (PC) are challenging, and there are still in gaps in the knowledge about its malignant progression. In particular, there is not enough information about the mechanism by which exosomes released by PC cells are significantly increased and involved in promoting malignant progression. Results In the present study, the expression of the metalloproteinase ADAM10 on cell membranes was found to be increased significantly in PC tissues and cell lines. Further, PC cells with high ADAM10 expression had stronger migration and invasion ability and were able to release more exosomes. Moreover, ADAM10 was found to affect the expression of RAB GTPase, a key regulatory molecule involved in the production of exosomes in cells, especially RAB5, which is associated with the formation of early endosomes. Further analysis indicated that ADAM10 may upregulate the transcription level of RAB5 by increasing the Notch2 signal intensity in PC cells, thus promoting the generation and secretion of exosomes in PC cells and further regulating the occurrence and development of PC. Conclusions These results reveal that ADAM10 plays a key role in regulating exosome secretion and may have potential as a therapeutic target for the clinical treatment of PC.