JAC1 suppresses proliferation of breast cancer through the JWA/p38/SMURF1/HER2 signaling

JAC1 suppresses proliferation of breast cancer through the JWA/p38/SMURF1/HER2 signaling

Abstract The overexpression of HER2 is associated with a malignant proliferation of breast cancer. In this study, we developed a non-cytotoxic JWA gene activating compound 1 (JAC1) to inhibit the proliferation of HER2-positive breast cancer cells in vitro and in vivo experimental models. JAC1 increa...

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Main Authors: Yanlin Ren, Dongyin Chen, Zurong Zhai, Junjie Chen, Aiping Li, Yan Liang, Jianwei Zhou
Format: Article
Language:English
Published: Nature Publishing Group 2021-04-01
Series:Cell Death Discovery
Online Access:https://doi.org/10.1038/s41420-021-00426-y
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spelling doaj-245d03474b4245eea4c5eea7c6fa57702021-04-25T11:47:04ZengNature Publishing GroupCell Death Discovery2058-77162021-04-017111310.1038/s41420-021-00426-yJAC1 suppresses proliferation of breast cancer through the JWA/p38/SMURF1/HER2 signalingYanlin Ren0Dongyin Chen1Zurong Zhai2Junjie Chen3Aiping Li4Yan Liang5Jianwei Zhou6Department of Molecular Cell Biology & Toxicology, Center for Global Health, School of Public Health, Nanjing Medical UniversityDepartment of Medicinal Chemistry, School of Pharmacy, Nanjing Medical UniversityDepartment of Molecular Cell Biology & Toxicology, Center for Global Health, School of Public Health, Nanjing Medical UniversityDepartment of Molecular Cell Biology & Toxicology, Center for Global Health, School of Public Health, Nanjing Medical UniversityDepartment of Molecular Cell Biology & Toxicology, Center for Global Health, School of Public Health, Nanjing Medical UniversityJiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Medicine, Nanjing Medical UniversityDepartment of Molecular Cell Biology & Toxicology, Center for Global Health, School of Public Health, Nanjing Medical UniversityAbstract The overexpression of HER2 is associated with a malignant proliferation of breast cancer. In this study, we developed a non-cytotoxic JWA gene activating compound 1 (JAC1) to inhibit the proliferation of HER2-positive breast cancer cells in vitro and in vivo experimental models. JAC1 increased the ubiquitination of HER2 at the K716 site through the E3 ubiquitin ligase SMURF1 which was due to the decreased expression of NEDD4, the E3 ubiquitin ligase of SMURF1. In conclusion, JAC1 suppresses the proliferation of HER2-positive breast cancer cells through the JWA triggered HER2 ubiquitination signaling. JAC1 may serve as a potential therapeutic agent for HER2-positive breast cancer.https://doi.org/10.1038/s41420-021-00426-y
collection DOAJ
language English
format Article
sources DOAJ
author Yanlin Ren
Dongyin Chen
Zurong Zhai
Junjie Chen
Aiping Li
Yan Liang
Jianwei Zhou
spellingShingle Yanlin Ren
Dongyin Chen
Zurong Zhai
Junjie Chen
Aiping Li
Yan Liang
Jianwei Zhou
JAC1 suppresses proliferation of breast cancer through the JWA/p38/SMURF1/HER2 signaling
Cell Death Discovery
author_facet Yanlin Ren
Dongyin Chen
Zurong Zhai
Junjie Chen
Aiping Li
Yan Liang
Jianwei Zhou
author_sort Yanlin Ren
title JAC1 suppresses proliferation of breast cancer through the JWA/p38/SMURF1/HER2 signaling
title_short JAC1 suppresses proliferation of breast cancer through the JWA/p38/SMURF1/HER2 signaling
title_full JAC1 suppresses proliferation of breast cancer through the JWA/p38/SMURF1/HER2 signaling
title_fullStr JAC1 suppresses proliferation of breast cancer through the JWA/p38/SMURF1/HER2 signaling
title_full_unstemmed JAC1 suppresses proliferation of breast cancer through the JWA/p38/SMURF1/HER2 signaling
title_sort jac1 suppresses proliferation of breast cancer through the jwa/p38/smurf1/her2 signaling
publisher Nature Publishing Group
series Cell Death Discovery
issn 2058-7716
publishDate 2021-04-01
description Abstract The overexpression of HER2 is associated with a malignant proliferation of breast cancer. In this study, we developed a non-cytotoxic JWA gene activating compound 1 (JAC1) to inhibit the proliferation of HER2-positive breast cancer cells in vitro and in vivo experimental models. JAC1 increased the ubiquitination of HER2 at the K716 site through the E3 ubiquitin ligase SMURF1 which was due to the decreased expression of NEDD4, the E3 ubiquitin ligase of SMURF1. In conclusion, JAC1 suppresses the proliferation of HER2-positive breast cancer cells through the JWA triggered HER2 ubiquitination signaling. JAC1 may serve as a potential therapeutic agent for HER2-positive breast cancer.
url https://doi.org/10.1038/s41420-021-00426-y
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