Connecting extracellular vesicle uptake and exosome biogenesis: intercellular communication in breast cancer cells is ITGB3-dependent

ABSTRACT: Metastasis, the spread of malignant cells from the primary tumour to distant sites is in 90% of the cases, the ultimate cause cancer related death. The integrin ITGB3 has been previously described to play an essential role in breast cancer metastasis, but the precise mechanisms remain undefined. We have now uncovered essential and thus far unknown roles of ITGB3 in vesicle uptake and exosome biogenesis. The functional requirement on ITGB3 is founded in its described interactions with heparan sulphated glyco-proteins (HSPGs) and the process of integrin recycling, allowing the capture of extracellular vesicles and their endocytosis-mediated internalisation. Key for the function of ITGB3 is the interaction and activation of the focal adhesion kinase (FAK), which is required for endocytosis of this vesicles and the entry of the endocytosis derived early endosomes into the exosome biogenesis pathway. Thus, ITGB3 has a central role in intracellular communication via extracellular vesicles, proposed to be critical for cancer metastasis.

INSTRUMENT(S): LTQ Orbitrap Velos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Extracellular Exosome Assembly

DISEASE(S): Breast Cancer

SUBMITTER: Eva Borràs  

LAB HEAD: Eduard Sabido

PROVIDER: PXD013489 | Pride | 2020-07-14

REPOSITORIES: Pride