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Targeting Lipocalin-2 in Inflammatory Breast Cancer Cells with Small Interference RNA and Small Molecule Inhibitors

Inflammatory Breast Cancer (IBC) is an aggressive form of invasive breast cancer, highly metastatic, representing 2–4% of all breast cancer cases in the United States. Despite its rare nature, IBC is responsible for 7–10% of all breast cancer deaths, with a 5-year survival rate of 40%. Thus, targete...

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Autores principales: Santiago-Sánchez, Ginette S., Noriega-Rivera, Ricardo, Hernández-O’Farrill, Eliud, Valiyeva, Fatma, Quiñones-Diaz, Blanca, Villodre, Emilly S., Debeb, Bisrat G., Rosado-Albacarys, Andrea, Vivas-Mejía, Pablo E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8395282/
https://www.ncbi.nlm.nih.gov/pubmed/34445288
http://dx.doi.org/10.3390/ijms22168581
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author Santiago-Sánchez, Ginette S.
Noriega-Rivera, Ricardo
Hernández-O’Farrill, Eliud
Valiyeva, Fatma
Quiñones-Diaz, Blanca
Villodre, Emilly S.
Debeb, Bisrat G.
Rosado-Albacarys, Andrea
Vivas-Mejía, Pablo E.
author_facet Santiago-Sánchez, Ginette S.
Noriega-Rivera, Ricardo
Hernández-O’Farrill, Eliud
Valiyeva, Fatma
Quiñones-Diaz, Blanca
Villodre, Emilly S.
Debeb, Bisrat G.
Rosado-Albacarys, Andrea
Vivas-Mejía, Pablo E.
author_sort Santiago-Sánchez, Ginette S.
collection PubMed
description Inflammatory Breast Cancer (IBC) is an aggressive form of invasive breast cancer, highly metastatic, representing 2–4% of all breast cancer cases in the United States. Despite its rare nature, IBC is responsible for 7–10% of all breast cancer deaths, with a 5-year survival rate of 40%. Thus, targeted and effective therapies against IBC are needed. Here, we proposed Lipocalin-2 (LCN2)—a secreted glycoprotein aberrantly abundant in different cancers—as a plausible target for IBC. In immunoblotting, we observed higher LCN2 protein levels in IBC cells than non-IBC cells, where the LCN2 levels were almost undetectable. We assessed the biological effects of targeting LCN2 in IBC cells with small interference RNAs (siRNAs) and small molecule inhibitors. siRNA-mediated LCN2 silencing in IBC cells significantly reduced cell proliferation, viability, migration, and invasion. Furthermore, LCN2 silencing promoted apoptosis and arrested the cell cycle progression in the G0/G1 to S phase transition. We used in silico analysis with a library of 25,000 compounds to identify potential LCN2 inhibitors, and four out of sixteen selected compounds significantly decreased cell proliferation, cell viability, and the AKT phosphorylation levels in SUM149 cells. Moreover, ectopically expressing LCN2 MCF7 cells, treated with two potential LCN2 inhibitors (ZINC00784494 and ZINC00640089) showed a significant decrease in cell proliferation. Our findings suggest LCN2 as a promising target for IBC treatment using siRNA and small molecule inhibitors.
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spelling pubmed-83952822021-08-28 Targeting Lipocalin-2 in Inflammatory Breast Cancer Cells with Small Interference RNA and Small Molecule Inhibitors Santiago-Sánchez, Ginette S. Noriega-Rivera, Ricardo Hernández-O’Farrill, Eliud Valiyeva, Fatma Quiñones-Diaz, Blanca Villodre, Emilly S. Debeb, Bisrat G. Rosado-Albacarys, Andrea Vivas-Mejía, Pablo E. Int J Mol Sci Article Inflammatory Breast Cancer (IBC) is an aggressive form of invasive breast cancer, highly metastatic, representing 2–4% of all breast cancer cases in the United States. Despite its rare nature, IBC is responsible for 7–10% of all breast cancer deaths, with a 5-year survival rate of 40%. Thus, targeted and effective therapies against IBC are needed. Here, we proposed Lipocalin-2 (LCN2)—a secreted glycoprotein aberrantly abundant in different cancers—as a plausible target for IBC. In immunoblotting, we observed higher LCN2 protein levels in IBC cells than non-IBC cells, where the LCN2 levels were almost undetectable. We assessed the biological effects of targeting LCN2 in IBC cells with small interference RNAs (siRNAs) and small molecule inhibitors. siRNA-mediated LCN2 silencing in IBC cells significantly reduced cell proliferation, viability, migration, and invasion. Furthermore, LCN2 silencing promoted apoptosis and arrested the cell cycle progression in the G0/G1 to S phase transition. We used in silico analysis with a library of 25,000 compounds to identify potential LCN2 inhibitors, and four out of sixteen selected compounds significantly decreased cell proliferation, cell viability, and the AKT phosphorylation levels in SUM149 cells. Moreover, ectopically expressing LCN2 MCF7 cells, treated with two potential LCN2 inhibitors (ZINC00784494 and ZINC00640089) showed a significant decrease in cell proliferation. Our findings suggest LCN2 as a promising target for IBC treatment using siRNA and small molecule inhibitors. MDPI 2021-08-10 /pmc/articles/PMC8395282/ /pubmed/34445288 http://dx.doi.org/10.3390/ijms22168581 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Santiago-Sánchez, Ginette S.
Noriega-Rivera, Ricardo
Hernández-O’Farrill, Eliud
Valiyeva, Fatma
Quiñones-Diaz, Blanca
Villodre, Emilly S.
Debeb, Bisrat G.
Rosado-Albacarys, Andrea
Vivas-Mejía, Pablo E.
Targeting Lipocalin-2 in Inflammatory Breast Cancer Cells with Small Interference RNA and Small Molecule Inhibitors
title Targeting Lipocalin-2 in Inflammatory Breast Cancer Cells with Small Interference RNA and Small Molecule Inhibitors
title_full Targeting Lipocalin-2 in Inflammatory Breast Cancer Cells with Small Interference RNA and Small Molecule Inhibitors
title_fullStr Targeting Lipocalin-2 in Inflammatory Breast Cancer Cells with Small Interference RNA and Small Molecule Inhibitors
title_full_unstemmed Targeting Lipocalin-2 in Inflammatory Breast Cancer Cells with Small Interference RNA and Small Molecule Inhibitors
title_short Targeting Lipocalin-2 in Inflammatory Breast Cancer Cells with Small Interference RNA and Small Molecule Inhibitors
title_sort targeting lipocalin-2 in inflammatory breast cancer cells with small interference rna and small molecule inhibitors
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8395282/
https://www.ncbi.nlm.nih.gov/pubmed/34445288
http://dx.doi.org/10.3390/ijms22168581
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