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Silencing of casein kinase 1 delta reduces migration and metastasis of triple negative breast cancer cells

The casein kinase 1 delta (CSNK1D) is a conserved serine/threonine protein kinase that regulates diverse cellular processes including cell cycle progression, circadian rhythm, and neurite outgrowth. Aberrant expression of CSNK1D is described in several cancer types including breast cancer, where it...

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Autores principales: Bar, Isabelle, Merhi, Ahmad, Larbanoix, Lionel, Constant, Manuel, Haussy, Sandy, Laurent, Sophie, Canon, Jean-Luc, Delrée, Paul
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6089398/
https://www.ncbi.nlm.nih.gov/pubmed/30112110
http://dx.doi.org/10.18632/oncotarget.25738
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author Bar, Isabelle
Merhi, Ahmad
Larbanoix, Lionel
Constant, Manuel
Haussy, Sandy
Laurent, Sophie
Canon, Jean-Luc
Delrée, Paul
author_facet Bar, Isabelle
Merhi, Ahmad
Larbanoix, Lionel
Constant, Manuel
Haussy, Sandy
Laurent, Sophie
Canon, Jean-Luc
Delrée, Paul
author_sort Bar, Isabelle
collection PubMed
description The casein kinase 1 delta (CSNK1D) is a conserved serine/threonine protein kinase that regulates diverse cellular processes including cell cycle progression, circadian rhythm, and neurite outgrowth. Aberrant expression of CSNK1D is described in several cancer types including breast cancer, where it is amplified in about 30% of triple negative breast (TNBC). Here, we have investigated the function of CSNK1D in triple negative cancer cell migration and metastasis. By using immunohistochemistry and in situ hybridization, we found that CNSK1D is highly expressed in primary tumor cells and in tumor cells invading lymphatic nodes compared to non-metastatic tumors. In vitro, knock-down of CSNK1D expression with specific shRNAs in the breast cancer cell line MDA-MB-231 markedly inhibited cancer cell proliferation, invasion and migration and affected the expression of the tight junction proteins claudin 1, occludin and the junction adhesion molecule A. In vivo, the inactivation of CSNK1D reduced lung metastasis in MDA-MB-231 breast cancer xenografts. Altogether, our results indicate that the downregulation of CSNK1D expression inhibits the proliferation and reduces the migration and the metastasis of breast cancer cells. As numerous inhibitors of CSNK1D are currently under development, this might represent an attractive therapeutic target for the treatment of TNBC.
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spelling pubmed-60893982018-08-15 Silencing of casein kinase 1 delta reduces migration and metastasis of triple negative breast cancer cells Bar, Isabelle Merhi, Ahmad Larbanoix, Lionel Constant, Manuel Haussy, Sandy Laurent, Sophie Canon, Jean-Luc Delrée, Paul Oncotarget Research Paper The casein kinase 1 delta (CSNK1D) is a conserved serine/threonine protein kinase that regulates diverse cellular processes including cell cycle progression, circadian rhythm, and neurite outgrowth. Aberrant expression of CSNK1D is described in several cancer types including breast cancer, where it is amplified in about 30% of triple negative breast (TNBC). Here, we have investigated the function of CSNK1D in triple negative cancer cell migration and metastasis. By using immunohistochemistry and in situ hybridization, we found that CNSK1D is highly expressed in primary tumor cells and in tumor cells invading lymphatic nodes compared to non-metastatic tumors. In vitro, knock-down of CSNK1D expression with specific shRNAs in the breast cancer cell line MDA-MB-231 markedly inhibited cancer cell proliferation, invasion and migration and affected the expression of the tight junction proteins claudin 1, occludin and the junction adhesion molecule A. In vivo, the inactivation of CSNK1D reduced lung metastasis in MDA-MB-231 breast cancer xenografts. Altogether, our results indicate that the downregulation of CSNK1D expression inhibits the proliferation and reduces the migration and the metastasis of breast cancer cells. As numerous inhibitors of CSNK1D are currently under development, this might represent an attractive therapeutic target for the treatment of TNBC. Impact Journals LLC 2018-07-20 /pmc/articles/PMC6089398/ /pubmed/30112110 http://dx.doi.org/10.18632/oncotarget.25738 Text en Copyright: © 2018 Bar et al. http://creativecommons.org/licenses/by/3.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) (CC-BY), which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Research Paper
Bar, Isabelle
Merhi, Ahmad
Larbanoix, Lionel
Constant, Manuel
Haussy, Sandy
Laurent, Sophie
Canon, Jean-Luc
Delrée, Paul
Silencing of casein kinase 1 delta reduces migration and metastasis of triple negative breast cancer cells
title Silencing of casein kinase 1 delta reduces migration and metastasis of triple negative breast cancer cells
title_full Silencing of casein kinase 1 delta reduces migration and metastasis of triple negative breast cancer cells
title_fullStr Silencing of casein kinase 1 delta reduces migration and metastasis of triple negative breast cancer cells
title_full_unstemmed Silencing of casein kinase 1 delta reduces migration and metastasis of triple negative breast cancer cells
title_short Silencing of casein kinase 1 delta reduces migration and metastasis of triple negative breast cancer cells
title_sort silencing of casein kinase 1 delta reduces migration and metastasis of triple negative breast cancer cells
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6089398/
https://www.ncbi.nlm.nih.gov/pubmed/30112110
http://dx.doi.org/10.18632/oncotarget.25738
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