Downregulation of ATG5-dependent macroautophagy by chaperone-mediated autophagy promotes breast cancer cell metastasis
Abstract Recent data have shown that the expression of lysosome-associated membrane protein type 2 A (LAMP2A), the key protein in the chaperone-mediated autophagy (CMA) pathway, is elevated in breast tumor tissues. However, the exact effects and mechanisms of CMA during breast cancer metastasis rema...
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2017
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oai:doaj.org-article:8d630c7e06124d669ac68db0b284ed7a2021-12-02T15:05:37ZDownregulation of ATG5-dependent macroautophagy by chaperone-mediated autophagy promotes breast cancer cell metastasis10.1038/s41598-017-04994-x2045-2322https://doaj.org/article/8d630c7e06124d669ac68db0b284ed7a2017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-04994-xhttps://doaj.org/toc/2045-2322Abstract Recent data have shown that the expression of lysosome-associated membrane protein type 2 A (LAMP2A), the key protein in the chaperone-mediated autophagy (CMA) pathway, is elevated in breast tumor tissues. However, the exact effects and mechanisms of CMA during breast cancer metastasis remain largely unknown. In this study, we found that the LAMP2A protein level was significantly elevated in human breast cancer tissues, particularly in metastatic carcinoma. The increased LAMP2A level was also positively correlated with the histologic grade of ductal breast cancer. High LAMP2A levels also predicted shorter overall survival of breast cancer patients. Downregulation of CMA activity by LAMP2A knockdown significantly inhibited the growth and metastasis of both MDA-MB-231 and MDA-MB-468 breast cancer cells in vivo and in vitro, while upregulation of CMA activity by LAMP2A overexpression had the opposite effect. Mechanistically, we found that elevated CMA activity mediated increased growth and metastasis of human breast cancer cells by downregulating the activity of autophagy-related gene 5 (ATG5)-dependent macroautophagy. Collectively, these results indicate that the anti-macroautophagic property is a key feature of CMA-mediated tumorigenesis and metastasis and may, in some contexts, serve as an attractive target for breast cancer therapies.Qi HanYoucai DengSha ChenRui ChenMingzhen YangZhujun ZhangXiongshan SunWei WangYing HeFangjie WangXiaodong PanPeng LiWenjing LaiHongqin LuoPei HuangXiao GuanYafei DengJun YanXianjie XuYan WenAn ChenChuanmin HuXiaohui LiShuhui LiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017) |
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Medicine R Science Q |
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Medicine R Science Q Qi Han Youcai Deng Sha Chen Rui Chen Mingzhen Yang Zhujun Zhang Xiongshan Sun Wei Wang Ying He Fangjie Wang Xiaodong Pan Peng Li Wenjing Lai Hongqin Luo Pei Huang Xiao Guan Yafei Deng Jun Yan Xianjie Xu Yan Wen An Chen Chuanmin Hu Xiaohui Li Shuhui Li Downregulation of ATG5-dependent macroautophagy by chaperone-mediated autophagy promotes breast cancer cell metastasis |
| description |
Abstract Recent data have shown that the expression of lysosome-associated membrane protein type 2 A (LAMP2A), the key protein in the chaperone-mediated autophagy (CMA) pathway, is elevated in breast tumor tissues. However, the exact effects and mechanisms of CMA during breast cancer metastasis remain largely unknown. In this study, we found that the LAMP2A protein level was significantly elevated in human breast cancer tissues, particularly in metastatic carcinoma. The increased LAMP2A level was also positively correlated with the histologic grade of ductal breast cancer. High LAMP2A levels also predicted shorter overall survival of breast cancer patients. Downregulation of CMA activity by LAMP2A knockdown significantly inhibited the growth and metastasis of both MDA-MB-231 and MDA-MB-468 breast cancer cells in vivo and in vitro, while upregulation of CMA activity by LAMP2A overexpression had the opposite effect. Mechanistically, we found that elevated CMA activity mediated increased growth and metastasis of human breast cancer cells by downregulating the activity of autophagy-related gene 5 (ATG5)-dependent macroautophagy. Collectively, these results indicate that the anti-macroautophagic property is a key feature of CMA-mediated tumorigenesis and metastasis and may, in some contexts, serve as an attractive target for breast cancer therapies. |
| format |
article |
| author |
Qi Han Youcai Deng Sha Chen Rui Chen Mingzhen Yang Zhujun Zhang Xiongshan Sun Wei Wang Ying He Fangjie Wang Xiaodong Pan Peng Li Wenjing Lai Hongqin Luo Pei Huang Xiao Guan Yafei Deng Jun Yan Xianjie Xu Yan Wen An Chen Chuanmin Hu Xiaohui Li Shuhui Li |
| author_facet |
Qi Han Youcai Deng Sha Chen Rui Chen Mingzhen Yang Zhujun Zhang Xiongshan Sun Wei Wang Ying He Fangjie Wang Xiaodong Pan Peng Li Wenjing Lai Hongqin Luo Pei Huang Xiao Guan Yafei Deng Jun Yan Xianjie Xu Yan Wen An Chen Chuanmin Hu Xiaohui Li Shuhui Li |
| author_sort |
Qi Han |
| title |
Downregulation of ATG5-dependent macroautophagy by chaperone-mediated autophagy promotes breast cancer cell metastasis |
| title_short |
Downregulation of ATG5-dependent macroautophagy by chaperone-mediated autophagy promotes breast cancer cell metastasis |
| title_full |
Downregulation of ATG5-dependent macroautophagy by chaperone-mediated autophagy promotes breast cancer cell metastasis |
| title_fullStr |
Downregulation of ATG5-dependent macroautophagy by chaperone-mediated autophagy promotes breast cancer cell metastasis |
| title_full_unstemmed |
Downregulation of ATG5-dependent macroautophagy by chaperone-mediated autophagy promotes breast cancer cell metastasis |
| title_sort |
downregulation of atg5-dependent macroautophagy by chaperone-mediated autophagy promotes breast cancer cell metastasis |
| publisher |
Nature Portfolio |
| publishDate |
2017 |
| url |
https://doaj.org/article/8d630c7e06124d669ac68db0b284ed7a |
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