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Downregulation of reticulocalbin‐1 differentially facilitates apoptosis and necroptosis in human prostate cancer cells
Reticulocalbin 1 (RCN1), an endoplasmic reticulum (ER)‐resident Ca(2+)‐binding protein, is dysregulated in cancers, but its pathophysiological roles are largely unclear. Here, we demonstrate that RCN1 is overexpressed in clinical prostate cancer (PCa) samples, associated with cyclin B, not cyclin D1...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5891187/ https://www.ncbi.nlm.nih.gov/pubmed/29453900 http://dx.doi.org/10.1111/cas.13541 |
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author | Liu, Xiaofei Zhang, Nianzhao Wang, Dawei Zhu, Deyu Yuan, Quan Zhang, Xiulei Qian, Lilin Niu, Huanmin Lu, Yi Ren, Guijie Tian, Keli Yuan, Huiqing |
author_facet | Liu, Xiaofei Zhang, Nianzhao Wang, Dawei Zhu, Deyu Yuan, Quan Zhang, Xiulei Qian, Lilin Niu, Huanmin Lu, Yi Ren, Guijie Tian, Keli Yuan, Huiqing |
author_sort | Liu, Xiaofei |
collection | PubMed |
description | Reticulocalbin 1 (RCN1), an endoplasmic reticulum (ER)‐resident Ca(2+)‐binding protein, is dysregulated in cancers, but its pathophysiological roles are largely unclear. Here, we demonstrate that RCN1 is overexpressed in clinical prostate cancer (PCa) samples, associated with cyclin B, not cyclin D1 expression, compared to that of benign tissues in a Chinese Han population. Downregulation of endogenous RCN1 significantly suppresses PCa cell viability and arrests the cell cycles of DU145 and LNCaP cells at the S and G2/M phases, respectively. RCN1 depletion causes ER stress, which is evidenced by induction of GRP78, activation of PERK and phosphorylation of eIF2α in PCa cells. Remarkably, RCN1 loss triggers DU145 cell apoptosis in a caspase‐dependent manner but mainly causes necroptosis in LNCaP cells. An animal‐based analysis confirms that RCN1 depletion suppresses cell proliferation and promotes cell death. Further investigations reveal that RCN1 depletion leads to elevation of phosphatase and tensin homolog (PTEN) and inactivation of AKT in DU145 cells. Silencing of PTEN partially restores apoptotic cells upon RCN1 loss. In LNCaP cells, predominant activation of CaMKII is important for necroptosis in response to RCN1 depletion. Thus, RCN1 may promote cell survival and serve as a useful target for cancer therapy. |
format | Online Article Text |
id | pubmed-5891187 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-58911872018-04-13 Downregulation of reticulocalbin‐1 differentially facilitates apoptosis and necroptosis in human prostate cancer cells Liu, Xiaofei Zhang, Nianzhao Wang, Dawei Zhu, Deyu Yuan, Quan Zhang, Xiulei Qian, Lilin Niu, Huanmin Lu, Yi Ren, Guijie Tian, Keli Yuan, Huiqing Cancer Sci Original Articles Reticulocalbin 1 (RCN1), an endoplasmic reticulum (ER)‐resident Ca(2+)‐binding protein, is dysregulated in cancers, but its pathophysiological roles are largely unclear. Here, we demonstrate that RCN1 is overexpressed in clinical prostate cancer (PCa) samples, associated with cyclin B, not cyclin D1 expression, compared to that of benign tissues in a Chinese Han population. Downregulation of endogenous RCN1 significantly suppresses PCa cell viability and arrests the cell cycles of DU145 and LNCaP cells at the S and G2/M phases, respectively. RCN1 depletion causes ER stress, which is evidenced by induction of GRP78, activation of PERK and phosphorylation of eIF2α in PCa cells. Remarkably, RCN1 loss triggers DU145 cell apoptosis in a caspase‐dependent manner but mainly causes necroptosis in LNCaP cells. An animal‐based analysis confirms that RCN1 depletion suppresses cell proliferation and promotes cell death. Further investigations reveal that RCN1 depletion leads to elevation of phosphatase and tensin homolog (PTEN) and inactivation of AKT in DU145 cells. Silencing of PTEN partially restores apoptotic cells upon RCN1 loss. In LNCaP cells, predominant activation of CaMKII is important for necroptosis in response to RCN1 depletion. Thus, RCN1 may promote cell survival and serve as a useful target for cancer therapy. John Wiley and Sons Inc. 2018-03-31 2018-04 /pmc/articles/PMC5891187/ /pubmed/29453900 http://dx.doi.org/10.1111/cas.13541 Text en © 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
spellingShingle | Original Articles Liu, Xiaofei Zhang, Nianzhao Wang, Dawei Zhu, Deyu Yuan, Quan Zhang, Xiulei Qian, Lilin Niu, Huanmin Lu, Yi Ren, Guijie Tian, Keli Yuan, Huiqing Downregulation of reticulocalbin‐1 differentially facilitates apoptosis and necroptosis in human prostate cancer cells |
title | Downregulation of reticulocalbin‐1 differentially facilitates apoptosis and necroptosis in human prostate cancer cells |
title_full | Downregulation of reticulocalbin‐1 differentially facilitates apoptosis and necroptosis in human prostate cancer cells |
title_fullStr | Downregulation of reticulocalbin‐1 differentially facilitates apoptosis and necroptosis in human prostate cancer cells |
title_full_unstemmed | Downregulation of reticulocalbin‐1 differentially facilitates apoptosis and necroptosis in human prostate cancer cells |
title_short | Downregulation of reticulocalbin‐1 differentially facilitates apoptosis and necroptosis in human prostate cancer cells |
title_sort | downregulation of reticulocalbin‐1 differentially facilitates apoptosis and necroptosis in human prostate cancer cells |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5891187/ https://www.ncbi.nlm.nih.gov/pubmed/29453900 http://dx.doi.org/10.1111/cas.13541 |
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