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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...

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Autores principales: Xu, Cheng, Cao, Lu, Liu, Jianhua, Qian, Zhongrun, Peng, Yu, Zhu, Wenjing, Qiu, Yongming, Lin, Yingying
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cognizant Communication Corporation 2017
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.
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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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