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Endostatin induces autophagy in endothelial cells by modulating Beclin 1 and beta-catenin levels.


ABSTRACT: Endostatin is a well-characterized endogenous inhibitor of angiogenesis that affects cell proliferation and migration by inhibiting integrin and Wnt-mediated signalling pathways. Here, we show that endothelial cells treated with native and P125A-endostatin activate autophagy. Because autophagy can either be protective or induce programmed cell death, experiments were carried out to understand the signalling pathways leading to autophagy in endothelial cells. P125A-endostatin treatment increased the levels of Beclin 1, a crucial molecule in vesicle nucleation and autophagy. The treatment also reduced the levels of Bcl-2, Bcl-x(L) and beta-catenin; however, progressively increasing amounts of Bcl-2 and Bcl-x(L) were found to be complexed with Beclin 1. Increased beta-catenin and Wnt-mediated signalling reduced Beclin 1 levels and rescued endothelial cells from endostatin-induced autophagy. Finally, knocking down Beclin 1 levels by RNA interference decreased autophagy and accelerated caspase activation in endostatin-treated cells. These studies suggest that endothelial cells may initiate autophagy as a survival response to limit the effects of angiogenesis inhibitors. Thus, interfering with autophagy can potentiate the effects of endostatin by promoting a switch to apoptosis.

SUBMITTER: Nguyen TM 

PROVIDER: S-EPMC4516517 | biostudies-literature | 2009 Sep

REPOSITORIES: biostudies-literature

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Endostatin induces autophagy in endothelial cells by modulating Beclin 1 and beta-catenin levels.

Nguyen Tri Minh Bui TM   Subramanian Indira V IV   Xiao Xue X   Ghosh Goutam G   Nguyen Phan P   Kelekar Ameeta A   Ramakrishnan S S  

Journal of cellular and molecular medicine 20090227 9B


Endostatin is a well-characterized endogenous inhibitor of angiogenesis that affects cell proliferation and migration by inhibiting integrin and Wnt-mediated signalling pathways. Here, we show that endothelial cells treated with native and P125A-endostatin activate autophagy. Because autophagy can either be protective or induce programmed cell death, experiments were carried out to understand the signalling pathways leading to autophagy in endothelial cells. P125A-endostatin treatment increased  ...[more]

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