2012
DOI: 10.1172/jci64537
|View full text |Cite
|
Sign up to set email alerts
|

Endothelial epsin deficiency decreases tumor growth by enhancing VEGF signaling

Abstract: Epsins are a family of ubiquitin-binding, endocytic clathrin adaptors. Mice lacking both epsins 1 and 2 (Epn1/2) die at embryonic day 10 and exhibit an abnormal vascular phenotype. To examine the angiogenic role of endothelial epsins, we generated mice with constitutive or inducible deletion of Epn1/2 in vascular endothelium. These mice exhibited no abnormal phenotypes under normal conditions, suggesting that lack of endothelial epsins 1 and 2 did not affect normal blood vessels. In tumors, however, loss of ep… Show more

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
3
1

Citation Types

18
238
1
2

Year Published

2016
2016
2022
2022

Publication Types

Select...
4
3

Relationship

0
7

Authors

Journals

citations
Cited by 107 publications
(259 citation statements)
references
References 39 publications
(46 reference statements)
18
238
1
2
Order By: Relevance
“…Our data suggest that CME is not required for VEGF signalling to ERK1/2 or to Akt, whereas macropinocytosis is crucial. This finding is consistent with previous studies showing that CME is not essential for VEGF-mediated activation of the downstream signalling cascades (Bruns et al, 2010;Lampugnani et al, 2006;Lee et al, 2014;Pasula et al, 2012;Tessneer et al, 2014). However, in contrast to these data, other studies have reported that CME is required for VEGF-mediated downstream signalling (Gourlaouen et al, 2013;Nakayama et al, 2013).…”
Section: Discussionsupporting
confidence: 92%
See 2 more Smart Citations
“…Our data suggest that CME is not required for VEGF signalling to ERK1/2 or to Akt, whereas macropinocytosis is crucial. This finding is consistent with previous studies showing that CME is not essential for VEGF-mediated activation of the downstream signalling cascades (Bruns et al, 2010;Lampugnani et al, 2006;Lee et al, 2014;Pasula et al, 2012;Tessneer et al, 2014). However, in contrast to these data, other studies have reported that CME is required for VEGF-mediated downstream signalling (Gourlaouen et al, 2013;Nakayama et al, 2013).…”
Section: Discussionsupporting
confidence: 92%
“…2014). However, intriguingly, several studies have reported that VEGFR2 degradation persists even when the clathrin pathway is blocked (Bhattacharya et al, 2005;Fearnley et al, 2016;Gourlaouen et al, 2013;Pasula et al, 2012;Tessneer et al, 2014), which suggests that VEGFR2 is also internalised through a route that is independent of clathrin. Indeed, the data presented here suggest that, following activation with VEGF, the preferred route of endocytosis of VEGFR2 is macropinocytosis, whereas, unexpectedly, only a minor fraction of VEGFR2 internalises by CME.…”
Section: Discussionmentioning
confidence: 99%
See 1 more Smart Citation
“…Then, in the absence of the inhibitors, the cells were stimulated with VEGF for the indicated time intervals, lysed, and analyzed by immunoblotting using antibodies against VEGFR2, p-ERK1/2, p-Akt, ERK1/2, or Akt. In the presence of VEGF, there is a progressive decrease of the levels of VEGFR2, which must be due to VEGF-induced internalization of the receptor, followed by its degradation in lysosomes (13,18,20). Quantification of p-ERK and p-Akt is shown in the graphs below the immunoblots (n ϭ 3, mean Ϯ S.D., *, p Ͻ 0.05; **, p Ͻ 0.01; ***, p Ͻ 0.001, ANOVA).…”
Section: Discussionmentioning
confidence: 99%
“…Similarly to other receptor-tyrosine kinases, activation of VEGFR2 by VEGF results in receptor internalization into the endocytic compartments (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24). However, unlike the typical activation-dependent internalization of receptor-tyrosine kinases, VEGFR2 undergoes efficient endocytosis even in the absence of VEGF (13,25,26), via the clathrin-mediated route (13).…”
mentioning
confidence: 99%