Cargando…

Hypoxia-inducible factor-1α and Wnt/β-catenin signaling pathways promote the invasion of hypoxic gastric cancer cells

The present study aimed to examine the association between hypoxia-inducible factor (HIF)-1α and the Wnt/β-catenin signaling pathway in a hypoxic environment. The study also aimed to explore the possible mechanisms underlying the invasion of hypoxic gastric cancer cells in vitro and in vivo. The pcD...

Descripción completa

Detalles Bibliográficos
Autores principales: LIU, HONG-LAN, LIU, DANG, DING, GUANG-RONG, LIAO, PENG-FEI, ZHANG, JUN-WEN
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4526080/
https://www.ncbi.nlm.nih.gov/pubmed/25997455
http://dx.doi.org/10.3892/mmr.2015.3812
_version_ 1782384380231024640
author LIU, HONG-LAN
LIU, DANG
DING, GUANG-RONG
LIAO, PENG-FEI
ZHANG, JUN-WEN
author_facet LIU, HONG-LAN
LIU, DANG
DING, GUANG-RONG
LIAO, PENG-FEI
ZHANG, JUN-WEN
author_sort LIU, HONG-LAN
collection PubMed
description The present study aimed to examine the association between hypoxia-inducible factor (HIF)-1α and the Wnt/β-catenin signaling pathway in a hypoxic environment. The study also aimed to explore the possible mechanisms underlying the invasion of hypoxic gastric cancer cells in vitro and in vivo. The pcDNA™ 6.2-GW/EmGFP-miR-β-catenin plasmid was transfected into SGC-7901 gastric cancer cells, resulting in cells with stable suppression of β-catenin expression. The biological characteristics of the control, liposome, negative control, β-catenin knockdown, hypoxia and hypoxia β-catenin knockdown groups were tested using an invasion assay. The differences in the invasive capacity of the control, negative control and liposome groups were not statistically significant. However, the hypoxia group demonstrated a significantly enhanced invasive capacity, as compared with that in the control group (P<0.05). In the hypoxia β-catenin knockdown group, reduced cell penetration and diminished invasive behavior was observed (P<0.05). In the hypoxia and double (chemical + physical) hypoxia groups, HIF-1α, β-catenin, urokinase-type plasminogen activator (uPA) and matrix metalloproteinase (MMP-7) protein and mRNA expression levels were elevated. In response to knockdown of β-catenin expression, HIF-1α, β-catenin, uPA and MMP-7 protein as well as mRNA expression levels were significantly reduced in the hypoxia β-catenin knockdown and the double hypoxia β-catenin knockdown groups. In an in vivo experiment, the growth rate of xenograft tumors of hypoxic and control cells was high alongside increased HIF-1α, β-catenin, uPA and MMP-7 levels according to western blot and immunohistochemical analyses, while growth and protein levels of tumors from hypoxic β-catenin knockdown cells were significantly lower and those of β-catenin knockdown cells were lowest. In conclusion, these results suggested that HIF-1α activation was able to regulate the Wnt/β-catenin pathway, and that HIF-1α may be controlled by the Wnt/β-catenin pathway. A potential mechanism underlying SGC-7901 tumorigenicity is the activation of the Wnt/β-catenin signaling pathway, which activates uPA and MMP-7 expression and contributes to the enhanced invasion of hypoxic cancer cells.
format Online
Article
Text
id pubmed-4526080
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher D.A. Spandidos
record_format MEDLINE/PubMed
spelling pubmed-45260802015-11-30 Hypoxia-inducible factor-1α and Wnt/β-catenin signaling pathways promote the invasion of hypoxic gastric cancer cells LIU, HONG-LAN LIU, DANG DING, GUANG-RONG LIAO, PENG-FEI ZHANG, JUN-WEN Mol Med Rep Articles The present study aimed to examine the association between hypoxia-inducible factor (HIF)-1α and the Wnt/β-catenin signaling pathway in a hypoxic environment. The study also aimed to explore the possible mechanisms underlying the invasion of hypoxic gastric cancer cells in vitro and in vivo. The pcDNA™ 6.2-GW/EmGFP-miR-β-catenin plasmid was transfected into SGC-7901 gastric cancer cells, resulting in cells with stable suppression of β-catenin expression. The biological characteristics of the control, liposome, negative control, β-catenin knockdown, hypoxia and hypoxia β-catenin knockdown groups were tested using an invasion assay. The differences in the invasive capacity of the control, negative control and liposome groups were not statistically significant. However, the hypoxia group demonstrated a significantly enhanced invasive capacity, as compared with that in the control group (P<0.05). In the hypoxia β-catenin knockdown group, reduced cell penetration and diminished invasive behavior was observed (P<0.05). In the hypoxia and double (chemical + physical) hypoxia groups, HIF-1α, β-catenin, urokinase-type plasminogen activator (uPA) and matrix metalloproteinase (MMP-7) protein and mRNA expression levels were elevated. In response to knockdown of β-catenin expression, HIF-1α, β-catenin, uPA and MMP-7 protein as well as mRNA expression levels were significantly reduced in the hypoxia β-catenin knockdown and the double hypoxia β-catenin knockdown groups. In an in vivo experiment, the growth rate of xenograft tumors of hypoxic and control cells was high alongside increased HIF-1α, β-catenin, uPA and MMP-7 levels according to western blot and immunohistochemical analyses, while growth and protein levels of tumors from hypoxic β-catenin knockdown cells were significantly lower and those of β-catenin knockdown cells were lowest. In conclusion, these results suggested that HIF-1α activation was able to regulate the Wnt/β-catenin pathway, and that HIF-1α may be controlled by the Wnt/β-catenin pathway. A potential mechanism underlying SGC-7901 tumorigenicity is the activation of the Wnt/β-catenin signaling pathway, which activates uPA and MMP-7 expression and contributes to the enhanced invasion of hypoxic cancer cells. D.A. Spandidos 2015-09 2015-05-21 /pmc/articles/PMC4526080/ /pubmed/25997455 http://dx.doi.org/10.3892/mmr.2015.3812 Text en Copyright © 2015, Spandidos Publications http://creativecommons.org/licenses/by/3.0 This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited.
spellingShingle Articles
LIU, HONG-LAN
LIU, DANG
DING, GUANG-RONG
LIAO, PENG-FEI
ZHANG, JUN-WEN
Hypoxia-inducible factor-1α and Wnt/β-catenin signaling pathways promote the invasion of hypoxic gastric cancer cells
title Hypoxia-inducible factor-1α and Wnt/β-catenin signaling pathways promote the invasion of hypoxic gastric cancer cells
title_full Hypoxia-inducible factor-1α and Wnt/β-catenin signaling pathways promote the invasion of hypoxic gastric cancer cells
title_fullStr Hypoxia-inducible factor-1α and Wnt/β-catenin signaling pathways promote the invasion of hypoxic gastric cancer cells
title_full_unstemmed Hypoxia-inducible factor-1α and Wnt/β-catenin signaling pathways promote the invasion of hypoxic gastric cancer cells
title_short Hypoxia-inducible factor-1α and Wnt/β-catenin signaling pathways promote the invasion of hypoxic gastric cancer cells
title_sort hypoxia-inducible factor-1α and wnt/β-catenin signaling pathways promote the invasion of hypoxic gastric cancer cells
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4526080/
https://www.ncbi.nlm.nih.gov/pubmed/25997455
http://dx.doi.org/10.3892/mmr.2015.3812
work_keys_str_mv AT liuhonglan hypoxiainduciblefactor1aandwntbcateninsignalingpathwayspromotetheinvasionofhypoxicgastriccancercells
AT liudang hypoxiainduciblefactor1aandwntbcateninsignalingpathwayspromotetheinvasionofhypoxicgastriccancercells
AT dingguangrong hypoxiainduciblefactor1aandwntbcateninsignalingpathwayspromotetheinvasionofhypoxicgastriccancercells
AT liaopengfei hypoxiainduciblefactor1aandwntbcateninsignalingpathwayspromotetheinvasionofhypoxicgastriccancercells
AT zhangjunwen hypoxiainduciblefactor1aandwntbcateninsignalingpathwayspromotetheinvasionofhypoxicgastriccancercells