PMID- 23608754
OWN - NLM
STAT- MEDLINE
DCOM- 20130801
LR  - 20230216
IS  - 1530-0307 (Electronic)
IS  - 0023-6837 (Print)
IS  - 0023-6837 (Linking)
VI  - 93
IP  - 6
DP  - 2013 Jun
TI  - Autophagy mediates paracrine regulation of vascular endothelial cells.
PG  - 639-45
LID - 10.1038/labinvest.2013.57 [doi]
AB  - Gastrin-releasing peptide (GRP) is a proangiogenic ligand secreted by tumors and 
      acts directly upon binding to GRP receptor in endothelial cells. Angiogenesis 
      plays a critical role in the pathology of various diseases, including cancer, as 
      the formation of new blood vessels potentiates the rate of tumor growth and 
      dissemination. GRP increases the migration of endothelial cells, but much is 
      unknown about its role on endothelial cell proliferation and survival, as well as 
      the signaling pathways involved. In the present study, we showed that GRP 
      increases endothelial cell proliferation and tubule formation. There was a 
      time-dependent increase in the levels of phosphorylated AKT, mammalian target of 
      rapamycin (mTOR), and S6R in human umbilical vein endothelial cells treated with 
      GRP. Interestingly, GRP treatment decreased the expression of proautophagic 
      factors, ATG5, BECN1, and LC3 proteins. GRP also attenuated rapamycin-induced 
      formation of autophagosomes. Moreover, overexpression of ATG5 or BECN1 
      significantly decreased tubule formation induced by exogenous GRP, whereas siRNA 
      against ATG5 or BECN1 resulted in increased tubule formation with GRP treatment. 
      Our results show that GRP inhibits the process of autophagy in vascular 
      endothelial cells, thereby increasing endothelial cell proliferation and tubule 
      formation. Here, we describe a novel role of GRP in the regulation of autophagy 
      of endothelial cells, thereby providing a potential new therapeutic strategy in 
      targeting angiogenesis during cancer progression.
FAU - Kim, Kwang Woon
AU  - Kim KW
AD  - Department of Pediatric Surgery, Vanderbilt University Medical Center, Nashville, 
      TN, USA.
FAU - Paul, Pritha
AU  - Paul P
FAU - Qiao, Jingbo
AU  - Qiao J
FAU - Chung, Dai H
AU  - Chung DH
LA  - eng
GR  - R01 DK061470/DK/NIDDK NIH HHS/United States
GR  - R01 DK61470/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20130422
PL  - United States
TA  - Lab Invest
JT  - Laboratory investigation; a journal of technical methods and pathology
JID - 0376617
RN  - 0 (ATG5 protein, human)
RN  - 0 (Apoptosis Regulatory Proteins)
RN  - 0 (Autophagy-Related Protein 5)
RN  - 0 (BECN1 protein, human)
RN  - 0 (Beclin-1)
RN  - 0 (Membrane Proteins)
RN  - 0 (Microtubule-Associated Proteins)
RN  - 80043-53-4 (Gastrin-Releasing Peptide)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Apoptosis Regulatory Proteins/metabolism
MH  - *Autophagy
MH  - Autophagy-Related Protein 5
MH  - Beclin-1
MH  - *Cell Proliferation
MH  - Coculture Techniques
MH  - Endothelial Cells/*physiology
MH  - Endothelium, Vascular/growth & development
MH  - Gastrin-Releasing Peptide/*physiology
MH  - Gene Expression Regulation
MH  - Human Umbilical Vein Endothelial Cells
MH  - Humans
MH  - Membrane Proteins/metabolism
MH  - Microtubule-Associated Proteins/metabolism
MH  - *Neovascularization, Pathologic
MH  - Paracrine Communication
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Signal Transduction
MH  - TOR Serine-Threonine Kinases/metabolism
PMC - PMC3669233
MID - NIHMS453173
EDAT- 2013/04/24 06:00
MHDA- 2013/08/02 06:00
PMCR- 2013/12/01
CRDT- 2013/04/24 06:00
PHST- 2013/04/24 06:00 [entrez]
PHST- 2013/04/24 06:00 [pubmed]
PHST- 2013/08/02 06:00 [medline]
PHST- 2013/12/01 00:00 [pmc-release]
AID - S0023-6837(22)00931-X [pii]
AID - 10.1038/labinvest.2013.57 [doi]
PST - ppublish
SO  - Lab Invest. 2013 Jun;93(6):639-45. doi: 10.1038/labinvest.2013.57. Epub 2013 Apr 
      22.