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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...

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Autores principales: Karacicek, B., Erac, Y., Tosun, M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
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.
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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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