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Blockage of Orai1-Nucleolin interaction meditated calcium influx attenuates breast cancer cells growth
As an important second messenger, calcium (Ca(2+)) regulates a wide variety of physiological processes. Disturbance of intracellular calcium homeostasis implicated in the occurrence of multiple types of diseases. Orai1 is the major player in mediating store-operated calcium entry (SOCE) and regulate...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9478099/ https://www.ncbi.nlm.nih.gov/pubmed/36109490 http://dx.doi.org/10.1038/s41389-022-00429-z |
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author | Gu, Chunming Zhang, Wenhao Yang, Enze Gu, Congyou Zhang, Zhaoyang Ke, Jing Wang, Xiong Wu, Shengying Li, Shan Wu, Fuyun |
author_facet | Gu, Chunming Zhang, Wenhao Yang, Enze Gu, Congyou Zhang, Zhaoyang Ke, Jing Wang, Xiong Wu, Shengying Li, Shan Wu, Fuyun |
author_sort | Gu, Chunming |
collection | PubMed |
description | As an important second messenger, calcium (Ca(2+)) regulates a wide variety of physiological processes. Disturbance of intracellular calcium homeostasis implicated in the occurrence of multiple types of diseases. Orai1 is the major player in mediating store-operated calcium entry (SOCE) and regulates calcium homeostasis in non-excitable cells. Over-expression and activation of Orai1 have been reported in breast cancer. However, its molecular mechanisms are still not very clear. Here, we demonstrated that Nucleolin (NCL) was a novel interacting partner of Orai1. NCL is a multifunctional nucleocytoplasmic protein and is upregulated in human breast tumors. The binding of C-termini of NCL (NCL-CT) to N-termini of Orai1 (Orai1-NT) is critical for mediating calcium influx and proliferation of breast cancer cells. Blocking the NCL-Orai1 interaction by synthesized Orai1 peptide can effectively reduce the intracellular calcium influx and suppress the proliferation of breast cancer cells in vitro and in vivo. Our findings reveal a novel activation mechanism of Orai1 via direct interaction with NCL, which may lead to calcium homeostasis imbalance and promote the proliferation of breast cancer cells. Blocking NCL-Orai1 interaction might be an effective treatment of breast cancer. |
format | Online Article Text |
id | pubmed-9478099 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-94780992022-09-17 Blockage of Orai1-Nucleolin interaction meditated calcium influx attenuates breast cancer cells growth Gu, Chunming Zhang, Wenhao Yang, Enze Gu, Congyou Zhang, Zhaoyang Ke, Jing Wang, Xiong Wu, Shengying Li, Shan Wu, Fuyun Oncogenesis Article As an important second messenger, calcium (Ca(2+)) regulates a wide variety of physiological processes. Disturbance of intracellular calcium homeostasis implicated in the occurrence of multiple types of diseases. Orai1 is the major player in mediating store-operated calcium entry (SOCE) and regulates calcium homeostasis in non-excitable cells. Over-expression and activation of Orai1 have been reported in breast cancer. However, its molecular mechanisms are still not very clear. Here, we demonstrated that Nucleolin (NCL) was a novel interacting partner of Orai1. NCL is a multifunctional nucleocytoplasmic protein and is upregulated in human breast tumors. The binding of C-termini of NCL (NCL-CT) to N-termini of Orai1 (Orai1-NT) is critical for mediating calcium influx and proliferation of breast cancer cells. Blocking the NCL-Orai1 interaction by synthesized Orai1 peptide can effectively reduce the intracellular calcium influx and suppress the proliferation of breast cancer cells in vitro and in vivo. Our findings reveal a novel activation mechanism of Orai1 via direct interaction with NCL, which may lead to calcium homeostasis imbalance and promote the proliferation of breast cancer cells. Blocking NCL-Orai1 interaction might be an effective treatment of breast cancer. Nature Publishing Group UK 2022-09-15 /pmc/articles/PMC9478099/ /pubmed/36109490 http://dx.doi.org/10.1038/s41389-022-00429-z Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Gu, Chunming Zhang, Wenhao Yang, Enze Gu, Congyou Zhang, Zhaoyang Ke, Jing Wang, Xiong Wu, Shengying Li, Shan Wu, Fuyun Blockage of Orai1-Nucleolin interaction meditated calcium influx attenuates breast cancer cells growth |
title | Blockage of Orai1-Nucleolin interaction meditated calcium influx attenuates breast cancer cells growth |
title_full | Blockage of Orai1-Nucleolin interaction meditated calcium influx attenuates breast cancer cells growth |
title_fullStr | Blockage of Orai1-Nucleolin interaction meditated calcium influx attenuates breast cancer cells growth |
title_full_unstemmed | Blockage of Orai1-Nucleolin interaction meditated calcium influx attenuates breast cancer cells growth |
title_short | Blockage of Orai1-Nucleolin interaction meditated calcium influx attenuates breast cancer cells growth |
title_sort | blockage of orai1-nucleolin interaction meditated calcium influx attenuates breast cancer cells growth |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9478099/ https://www.ncbi.nlm.nih.gov/pubmed/36109490 http://dx.doi.org/10.1038/s41389-022-00429-z |
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