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Functional consequences of enhanced expression of STIM1 and Orai1 in Huh-7 hepatocellular carcinoma tumor-initiating cells
BACKGROUND: The endoplasmic reticulum (ER) Ca(2+) sensor, stromal interaction molecule1 (STIM1) activates the plasma membrane (PM) channel Orai1 in order to mediate store-operated Ca(2+) entry (SOCE) in response to ER store depletion. Enhanced expression of STIM1 in cancer tissue has been associated...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6668110/ https://www.ncbi.nlm.nih.gov/pubmed/31366337 http://dx.doi.org/10.1186/s12885-019-5947-z |
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author | Karacicek, B. Erac, Y. Tosun, M. |
author_facet | Karacicek, B. Erac, Y. Tosun, M. |
author_sort | Karacicek, B. |
collection | PubMed |
description | BACKGROUND: The endoplasmic reticulum (ER) Ca(2+) sensor, stromal interaction molecule1 (STIM1) activates the plasma membrane (PM) channel Orai1 in order to mediate store-operated Ca(2+) entry (SOCE) in response to ER store depletion. Enhanced expression of STIM1 in cancer tissue has been associated with poor patient prognosis. Therefore, this study investigated the functional consequences of enhanced expression of STIM1 and Orai1 in a tumor-initiating subpopulation of Huh-7 hepatocellular carcinoma (HCC) cells that express epithelial cell adhesion molecule (EpCAM) and Prominin 1 (CD133). METHODS: We performed qRT-PCR, intracellular Ca(2+) monitoring, protein analyses, and real-time cell proliferation assays on EpCAM(+)CD133(+) subpopulation of tumor-initiating Huh-7 HCC cells expressing high levels of STIM1 and/or Orai1. Statistical significance between the means of two groups was evaluated using unpaired Student’s t-test. RESULTS: Enhanced STIM1 expression significantly increased ER Ca(2+) release and proliferation rate of EpCAM(+)CD133(+) cells. CONCLUSION: STIM1 overexpression may facilitate cancer cell survival by increasing ER Ca(2+)-buffering capacity, which makes more Ca(2+) available for the cytosolic events, on the other hand, possibly preventing Ca(2+)-dependent enzymatic activity in mitochondria whose Ca(2+) uniporter requires much higher cytosolic Ca(2+) levels. |
format | Online Article Text |
id | pubmed-6668110 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-66681102019-08-05 Functional consequences of enhanced expression of STIM1 and Orai1 in Huh-7 hepatocellular carcinoma tumor-initiating cells Karacicek, B. Erac, Y. Tosun, M. BMC Cancer Research Article BACKGROUND: The endoplasmic reticulum (ER) Ca(2+) sensor, stromal interaction molecule1 (STIM1) activates the plasma membrane (PM) channel Orai1 in order to mediate store-operated Ca(2+) entry (SOCE) in response to ER store depletion. Enhanced expression of STIM1 in cancer tissue has been associated with poor patient prognosis. Therefore, this study investigated the functional consequences of enhanced expression of STIM1 and Orai1 in a tumor-initiating subpopulation of Huh-7 hepatocellular carcinoma (HCC) cells that express epithelial cell adhesion molecule (EpCAM) and Prominin 1 (CD133). METHODS: We performed qRT-PCR, intracellular Ca(2+) monitoring, protein analyses, and real-time cell proliferation assays on EpCAM(+)CD133(+) subpopulation of tumor-initiating Huh-7 HCC cells expressing high levels of STIM1 and/or Orai1. Statistical significance between the means of two groups was evaluated using unpaired Student’s t-test. RESULTS: Enhanced STIM1 expression significantly increased ER Ca(2+) release and proliferation rate of EpCAM(+)CD133(+) cells. CONCLUSION: STIM1 overexpression may facilitate cancer cell survival by increasing ER Ca(2+)-buffering capacity, which makes more Ca(2+) available for the cytosolic events, on the other hand, possibly preventing Ca(2+)-dependent enzymatic activity in mitochondria whose Ca(2+) uniporter requires much higher cytosolic Ca(2+) levels. BioMed Central 2019-07-31 /pmc/articles/PMC6668110/ /pubmed/31366337 http://dx.doi.org/10.1186/s12885-019-5947-z Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided 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 Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Article Karacicek, B. Erac, Y. Tosun, M. Functional consequences of enhanced expression of STIM1 and Orai1 in Huh-7 hepatocellular carcinoma tumor-initiating cells |
title | Functional consequences of enhanced expression of STIM1 and Orai1 in Huh-7 hepatocellular carcinoma tumor-initiating cells |
title_full | Functional consequences of enhanced expression of STIM1 and Orai1 in Huh-7 hepatocellular carcinoma tumor-initiating cells |
title_fullStr | Functional consequences of enhanced expression of STIM1 and Orai1 in Huh-7 hepatocellular carcinoma tumor-initiating cells |
title_full_unstemmed | Functional consequences of enhanced expression of STIM1 and Orai1 in Huh-7 hepatocellular carcinoma tumor-initiating cells |
title_short | Functional consequences of enhanced expression of STIM1 and Orai1 in Huh-7 hepatocellular carcinoma tumor-initiating cells |
title_sort | functional consequences of enhanced expression of stim1 and orai1 in huh-7 hepatocellular carcinoma tumor-initiating cells |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6668110/ https://www.ncbi.nlm.nih.gov/pubmed/31366337 http://dx.doi.org/10.1186/s12885-019-5947-z |
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