A Ca²⁺-stimulated exosome release pathway in cancer cells is regulated by Munc13-4.

ABSTRACT: Cancer cells secrete copious amounts of exosomes, and elevated intracellular Ca²⁺ is critical for tumor progression and metastasis, but the underlying cellular mechanisms are unknown. Munc13-4 is a Ca²⁺-dependent SNAP receptor- and Rab-binding protein required for Ca²⁺-dependent membrane fusion. Here we show that acute elevation of Ca²⁺ in cancer cells stimulated a fivefold increase in CD63⁺, CD9⁺, and ALIX⁺ exosome release that was eliminated by Munc13-4 knockdown and not restored by Ca²⁺ binding-deficient Munc13-4 mutants. Direct imaging of CD63-pHluorin exosome release confirmed its Munc13-4 dependence. Depletion of Munc13-4 in highly aggressive breast carcinoma MDA-MB-231 cells reduced the size of C

SUBMITTER: Messenger SW 

PROVIDER: S-EPMC6080937 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature