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Suppression of Asparaginyl Endopeptidase Inhibits Polyomavirus Middle T Antigen-Induced Tumor Formation and Metastasis
Elevated circulating asparaginyl endopeptidase (AEP), a novel lysosomal protease, has been found in breast cancer, and AEP is thus considered to be a prognostic factor in this disease. However, the pathological functions of circulating AEP in the development of breast cancer and the potential of AEP...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cognizant Communication Corporation
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7841005/ https://www.ncbi.nlm.nih.gov/pubmed/27660925 http://dx.doi.org/10.3727/096504016X14743350548249 |
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author | Xu, Cheng Cao, Lu Liu, Jianhua Qian, Zhongrun Peng, Yu Zhu, Wenjing Qiu, Yongming Lin, Yingying |
author_facet | Xu, Cheng Cao, Lu Liu, Jianhua Qian, Zhongrun Peng, Yu Zhu, Wenjing Qiu, Yongming Lin, Yingying |
author_sort | Xu, Cheng |
collection | PubMed |
description | Elevated circulating asparaginyl endopeptidase (AEP), a novel lysosomal protease, has been found in breast cancer, and AEP is thus considered to be a prognostic factor in this disease. However, the pathological functions of circulating AEP in the development of breast cancer and the potential of AEP-targeted therapy remain unclear. We used MMTV-PyVmT transgenic mice, which spontaneously develop mammary tumors. Western blotting showed overexpression of AEP in both primary tumor tissue and lung metastases compared to their normal counterparts. Moreover, the concentration of circulating AEP gradually increased in the serum during the development of mammary tumors. Purified AEP protein injected through the tail vein promoted tumor growth and mammary tumor metastasis and shortened survival, whereas AEP-specific small compound inhibitors (AEPIs) effectively suppressed tumor progression and prolonged host survival. Further analysis of the molecular mechanism revealed that AEP was important for PI3K/AKT pathway activation. Thus, an elevated serum AEP level was closely related to mammary cancer progression and metastasis, and AEP is a potential target for breast cancer therapy in the clinic. |
format | Online Article Text |
id | pubmed-7841005 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Cognizant Communication Corporation |
record_format | MEDLINE/PubMed |
spelling | pubmed-78410052021-02-16 Suppression of Asparaginyl Endopeptidase Inhibits Polyomavirus Middle T Antigen-Induced Tumor Formation and Metastasis Xu, Cheng Cao, Lu Liu, Jianhua Qian, Zhongrun Peng, Yu Zhu, Wenjing Qiu, Yongming Lin, Yingying Oncol Res Article Elevated circulating asparaginyl endopeptidase (AEP), a novel lysosomal protease, has been found in breast cancer, and AEP is thus considered to be a prognostic factor in this disease. However, the pathological functions of circulating AEP in the development of breast cancer and the potential of AEP-targeted therapy remain unclear. We used MMTV-PyVmT transgenic mice, which spontaneously develop mammary tumors. Western blotting showed overexpression of AEP in both primary tumor tissue and lung metastases compared to their normal counterparts. Moreover, the concentration of circulating AEP gradually increased in the serum during the development of mammary tumors. Purified AEP protein injected through the tail vein promoted tumor growth and mammary tumor metastasis and shortened survival, whereas AEP-specific small compound inhibitors (AEPIs) effectively suppressed tumor progression and prolonged host survival. Further analysis of the molecular mechanism revealed that AEP was important for PI3K/AKT pathway activation. Thus, an elevated serum AEP level was closely related to mammary cancer progression and metastasis, and AEP is a potential target for breast cancer therapy in the clinic. Cognizant Communication Corporation 2017-03-13 /pmc/articles/PMC7841005/ /pubmed/27660925 http://dx.doi.org/10.3727/096504016X14743350548249 Text en Copyright © 2017 Cognizant, LLC. http://creativecommons.org/licenses/by-nc-nd/4.0/ This article is licensed under a Creative Commons Attribution-NonCommercial NoDerivatives 4.0 International License. |
spellingShingle | Article Xu, Cheng Cao, Lu Liu, Jianhua Qian, Zhongrun Peng, Yu Zhu, Wenjing Qiu, Yongming Lin, Yingying Suppression of Asparaginyl Endopeptidase Inhibits Polyomavirus Middle T Antigen-Induced Tumor Formation and Metastasis |
title | Suppression of Asparaginyl Endopeptidase Inhibits Polyomavirus Middle T Antigen-Induced Tumor Formation and Metastasis |
title_full | Suppression of Asparaginyl Endopeptidase Inhibits Polyomavirus Middle T Antigen-Induced Tumor Formation and Metastasis |
title_fullStr | Suppression of Asparaginyl Endopeptidase Inhibits Polyomavirus Middle T Antigen-Induced Tumor Formation and Metastasis |
title_full_unstemmed | Suppression of Asparaginyl Endopeptidase Inhibits Polyomavirus Middle T Antigen-Induced Tumor Formation and Metastasis |
title_short | Suppression of Asparaginyl Endopeptidase Inhibits Polyomavirus Middle T Antigen-Induced Tumor Formation and Metastasis |
title_sort | suppression of asparaginyl endopeptidase inhibits polyomavirus middle t antigen-induced tumor formation and metastasis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7841005/ https://www.ncbi.nlm.nih.gov/pubmed/27660925 http://dx.doi.org/10.3727/096504016X14743350548249 |
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