RT Journal Article
SR Electronic
T1 An inverted Caveolin-1 topology defines a novel exosome secreted from prostate cancer cells
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.03.19.999441
DO 10.1101/2020.03.19.999441
A1 Nicholas Ariotti
A1 Yeping Wu
A1 Satomi Okano
A1 Yann Gambin
A1 Jordan Follett
A1 James Rae
A1 Charles Ferguson
A1 Rohan D. Teasdale
A1 Kirill Alexandrov
A1 Frederic A. Meunier
A1 Michelle M. Hill
A1 Robert G. Parton
YR 2020
UL http://biorxiv.org/content/early/2020/03/20/2020.03.19.999441.abstract
AB Caveolin-1 (Cav1) expression and secretion is associated with prostate cancer (PCa) disease progression but the mechanisms underpinning Cav1 release remain poorly understood. Numerous studies have shown Cav1 can be secreted within exosome-like vesicles, but antibody-mediated neutralization can mitigate PCa progression; this is suggestive of an inverted (non-exosomal) Cav1 topology. Here we show that Cav1 can be secreted from specific PCa types in an inverted vesicle-associated form consistent with the features of bioactive Cav1 secretion. Characterization of the isolated vesicles by electron microscopy, single molecule fluorescent microscopy and proteomics reveals they represent a novel class of exosomes ∼40 nm in diameter containing ∼50-60 copies of Cav1 and strikingly, are released via a non-canonical secretory autophagy pathway. This study provides novel insights into a mechanism whereby Cav1 translocates from a normal plasma membrane distribution to an inverted secreted form implicated in PCa disease progression.