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Semaphorin 5A Promotes Gastric Cancer Invasion/Metastasis via Urokinase-Type Plasminogen Activator/Phosphoinositide 3-Kinase/Protein Kinase B
BACKGROUND: Semaphorin 5A, a member of the semaphorin family, was originally identified as an axonal guidance factor functioning during neuronal development. Previously, we showed that the expression of semaphorin 5A might contribute to the metastasis of gastric cancer. However, less information is...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer US
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3731515/ https://www.ncbi.nlm.nih.gov/pubmed/23661031 http://dx.doi.org/10.1007/s10620-013-2666-1 |
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author | Pan, Guoqing Zhu, Zhu Huang, Jian Yang, Chenggang Yang, Ying Wang, Yingxia Tuo, Xiaoyu Su, Guomiao Zhang, Xiangling Yang, Zhi Liu, Tao |
author_facet | Pan, Guoqing Zhu, Zhu Huang, Jian Yang, Chenggang Yang, Ying Wang, Yingxia Tuo, Xiaoyu Su, Guomiao Zhang, Xiangling Yang, Zhi Liu, Tao |
author_sort | Pan, Guoqing |
collection | PubMed |
description | BACKGROUND: Semaphorin 5A, a member of the semaphorin family, was originally identified as an axonal guidance factor functioning during neuronal development. Previously, we showed that the expression of semaphorin 5A might contribute to the metastasis of gastric cancer. However, less information is currently available as to the involvement of uPA in the semaphorin 5A-induced metastasis and invasion of gastric cancer cells. AIM: The present study was designed to test whether semaphorin 5A mediates the invasion and metastasis of gastric cancer via PI3K/Akt/uPA signaling. METHODS: The semaphorin 5A-overexpressing cell was established from the gastric cancer cell line AGS. The effect of semaphorin 5A on the expression of uPA was evaluated by ELISA and Western blotting as well as RT-PCR assays, respectively. Synthetic or natural inhibitors and dominant-negative mutants were used to determine the hierarchical relationship between semaphorin 5A, PI3K/Akt and uPA in the invasion and metastasis of gastric cancer. RESULTS: Overpression of semaphorin 5A enhanced the expression of uPA, and synthetic or natural inhibitors of uPA abolished semaphorin 5A-induced cell migration and invasion. Semaphorin 5A overexpression promoted the phosphorylation of Akt. Blocking effects of PI3K/Akt using pharmacologic inhibitors, dominant-negative mutants abolished the ability of semaphorin 5A to induce uPA expression and cell invasion and migration. CONCLUSION: Semaphorin 5A could promote invasion and metastasis of gastric cancer through the PI3K/Akt/uPA signal transduction pathway. Semaphorin 5A and its regulated molecules could be the potential targets for cancer therapy. |
format | Online Article Text |
id | pubmed-3731515 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Springer US |
record_format | MEDLINE/PubMed |
spelling | pubmed-37315152013-08-02 Semaphorin 5A Promotes Gastric Cancer Invasion/Metastasis via Urokinase-Type Plasminogen Activator/Phosphoinositide 3-Kinase/Protein Kinase B Pan, Guoqing Zhu, Zhu Huang, Jian Yang, Chenggang Yang, Ying Wang, Yingxia Tuo, Xiaoyu Su, Guomiao Zhang, Xiangling Yang, Zhi Liu, Tao Dig Dis Sci Original Article BACKGROUND: Semaphorin 5A, a member of the semaphorin family, was originally identified as an axonal guidance factor functioning during neuronal development. Previously, we showed that the expression of semaphorin 5A might contribute to the metastasis of gastric cancer. However, less information is currently available as to the involvement of uPA in the semaphorin 5A-induced metastasis and invasion of gastric cancer cells. AIM: The present study was designed to test whether semaphorin 5A mediates the invasion and metastasis of gastric cancer via PI3K/Akt/uPA signaling. METHODS: The semaphorin 5A-overexpressing cell was established from the gastric cancer cell line AGS. The effect of semaphorin 5A on the expression of uPA was evaluated by ELISA and Western blotting as well as RT-PCR assays, respectively. Synthetic or natural inhibitors and dominant-negative mutants were used to determine the hierarchical relationship between semaphorin 5A, PI3K/Akt and uPA in the invasion and metastasis of gastric cancer. RESULTS: Overpression of semaphorin 5A enhanced the expression of uPA, and synthetic or natural inhibitors of uPA abolished semaphorin 5A-induced cell migration and invasion. Semaphorin 5A overexpression promoted the phosphorylation of Akt. Blocking effects of PI3K/Akt using pharmacologic inhibitors, dominant-negative mutants abolished the ability of semaphorin 5A to induce uPA expression and cell invasion and migration. CONCLUSION: Semaphorin 5A could promote invasion and metastasis of gastric cancer through the PI3K/Akt/uPA signal transduction pathway. Semaphorin 5A and its regulated molecules could be the potential targets for cancer therapy. Springer US 2013-05-10 2013 /pmc/articles/PMC3731515/ /pubmed/23661031 http://dx.doi.org/10.1007/s10620-013-2666-1 Text en © The Author(s) 2013 https://creativecommons.org/licenses/by-nc/2.5/ Open AccessThis article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited. The exclusive right to any commercial use of the article is with Springer. |
spellingShingle | Original Article Pan, Guoqing Zhu, Zhu Huang, Jian Yang, Chenggang Yang, Ying Wang, Yingxia Tuo, Xiaoyu Su, Guomiao Zhang, Xiangling Yang, Zhi Liu, Tao Semaphorin 5A Promotes Gastric Cancer Invasion/Metastasis via Urokinase-Type Plasminogen Activator/Phosphoinositide 3-Kinase/Protein Kinase B |
title | Semaphorin 5A Promotes Gastric Cancer Invasion/Metastasis via Urokinase-Type Plasminogen Activator/Phosphoinositide 3-Kinase/Protein Kinase B |
title_full | Semaphorin 5A Promotes Gastric Cancer Invasion/Metastasis via Urokinase-Type Plasminogen Activator/Phosphoinositide 3-Kinase/Protein Kinase B |
title_fullStr | Semaphorin 5A Promotes Gastric Cancer Invasion/Metastasis via Urokinase-Type Plasminogen Activator/Phosphoinositide 3-Kinase/Protein Kinase B |
title_full_unstemmed | Semaphorin 5A Promotes Gastric Cancer Invasion/Metastasis via Urokinase-Type Plasminogen Activator/Phosphoinositide 3-Kinase/Protein Kinase B |
title_short | Semaphorin 5A Promotes Gastric Cancer Invasion/Metastasis via Urokinase-Type Plasminogen Activator/Phosphoinositide 3-Kinase/Protein Kinase B |
title_sort | semaphorin 5a promotes gastric cancer invasion/metastasis via urokinase-type plasminogen activator/phosphoinositide 3-kinase/protein kinase b |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3731515/ https://www.ncbi.nlm.nih.gov/pubmed/23661031 http://dx.doi.org/10.1007/s10620-013-2666-1 |
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