MACC-1 Promotes Endothelium-Dependent Angiogenesis in Gastric Cancer by Activating TWIST1/VEGF-A Signal Pathway.

Endothelium-dependent angiogenesis is thought to be a crucial step in cancer progression. We previously reported that metastasis-associated in colon cancer-1 (MACC1) contributed to the vasculogenic mimicry in gastric cancer (GC), but it remains unknown whether MACC1 promotes endothelium-dependent an...

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Main Authors: Lin Wang, Rui Zhou, Yang Zhao, Shaoting Dong, Jingwen Zhang, Yuhao Luo, Na Huang, Min Shi, Jianping Bin, Yulin Liao, Wangjun Liao
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2016-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC4900635?pdf=render
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spelling doaj-ac9e091362634c03a09672b0860de7962020-11-25T02:47:03ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-01116e015713710.1371/journal.pone.0157137MACC-1 Promotes Endothelium-Dependent Angiogenesis in Gastric Cancer by Activating TWIST1/VEGF-A Signal Pathway.Lin WangRui ZhouYang ZhaoShaoting DongJingwen ZhangYuhao LuoNa HuangMin ShiJianping BinYulin LiaoWangjun LiaoEndothelium-dependent angiogenesis is thought to be a crucial step in cancer progression. We previously reported that metastasis-associated in colon cancer-1 (MACC1) contributed to the vasculogenic mimicry in gastric cancer (GC), but it remains unknown whether MACC1 promotes endothelium-dependent angiogenesis of GC and whether TWIST1 is involved in this process. In the present study, we detected MACC1 expression and microvessel density (MVD) by immunohistochemistry in 159 patients with stage I-III GC, and investigated the role of TWIST1 and vascular endothelial growth factor A (VEGF-A) in MACC1-induced endothelium-dependent angiogenesis using nude mice with GC xenografts, and human umbilical vein endothelial cells (HUVECs) that were co-cultured with conditioned media from overexpression and interference MACC1 GC cells. We found that MACC1 expression was positively correlated with an increased MVD and tumor recurrence in GC patients. In GC xenograft models, MACC1 elevated MVD and upregulated the expression of VEGF-A as well as accelerated tumor growth. In addition, MACC1 obviously increased the expression of TWIST1 and induced tube-like formation of HUVECs, whereas attenuation of TWIST1 suppressed the protein expression of VEGF-A and repealed the effect of MACC1 on tube formation. Our findings shed light on the function of MACC1 in endothelium-dependent angiogenesis of GC and suggest potential prognostic and therapeutic value.http://europepmc.org/articles/PMC4900635?pdf=render
collection DOAJ
language English
format Article
sources DOAJ
author Lin Wang
Rui Zhou
Yang Zhao
Shaoting Dong
Jingwen Zhang
Yuhao Luo
Na Huang
Min Shi
Jianping Bin
Yulin Liao
Wangjun Liao
spellingShingle Lin Wang
Rui Zhou
Yang Zhao
Shaoting Dong
Jingwen Zhang
Yuhao Luo
Na Huang
Min Shi
Jianping Bin
Yulin Liao
Wangjun Liao
MACC-1 Promotes Endothelium-Dependent Angiogenesis in Gastric Cancer by Activating TWIST1/VEGF-A Signal Pathway.
PLoS ONE
author_facet Lin Wang
Rui Zhou
Yang Zhao
Shaoting Dong
Jingwen Zhang
Yuhao Luo
Na Huang
Min Shi
Jianping Bin
Yulin Liao
Wangjun Liao
author_sort Lin Wang
title MACC-1 Promotes Endothelium-Dependent Angiogenesis in Gastric Cancer by Activating TWIST1/VEGF-A Signal Pathway.
title_short MACC-1 Promotes Endothelium-Dependent Angiogenesis in Gastric Cancer by Activating TWIST1/VEGF-A Signal Pathway.
title_full MACC-1 Promotes Endothelium-Dependent Angiogenesis in Gastric Cancer by Activating TWIST1/VEGF-A Signal Pathway.
title_fullStr MACC-1 Promotes Endothelium-Dependent Angiogenesis in Gastric Cancer by Activating TWIST1/VEGF-A Signal Pathway.
title_full_unstemmed MACC-1 Promotes Endothelium-Dependent Angiogenesis in Gastric Cancer by Activating TWIST1/VEGF-A Signal Pathway.
title_sort macc-1 promotes endothelium-dependent angiogenesis in gastric cancer by activating twist1/vegf-a signal pathway.
publisher Public Library of Science (PLoS)
series PLoS ONE
issn 1932-6203
publishDate 2016-01-01
description Endothelium-dependent angiogenesis is thought to be a crucial step in cancer progression. We previously reported that metastasis-associated in colon cancer-1 (MACC1) contributed to the vasculogenic mimicry in gastric cancer (GC), but it remains unknown whether MACC1 promotes endothelium-dependent angiogenesis of GC and whether TWIST1 is involved in this process. In the present study, we detected MACC1 expression and microvessel density (MVD) by immunohistochemistry in 159 patients with stage I-III GC, and investigated the role of TWIST1 and vascular endothelial growth factor A (VEGF-A) in MACC1-induced endothelium-dependent angiogenesis using nude mice with GC xenografts, and human umbilical vein endothelial cells (HUVECs) that were co-cultured with conditioned media from overexpression and interference MACC1 GC cells. We found that MACC1 expression was positively correlated with an increased MVD and tumor recurrence in GC patients. In GC xenograft models, MACC1 elevated MVD and upregulated the expression of VEGF-A as well as accelerated tumor growth. In addition, MACC1 obviously increased the expression of TWIST1 and induced tube-like formation of HUVECs, whereas attenuation of TWIST1 suppressed the protein expression of VEGF-A and repealed the effect of MACC1 on tube formation. Our findings shed light on the function of MACC1 in endothelium-dependent angiogenesis of GC and suggest potential prognostic and therapeutic value.
url http://europepmc.org/articles/PMC4900635?pdf=render
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