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The NFAT3/RERG Complex in Luminal Breast Cancers Is Required to Inhibit Cell Invasion and May Be Correlated With an Absence of Axillary Lymph Nodes Colonization

Luminal breast cancers represent 70% of newly diagnosed breast cancers per annum and have a relatively good prognosis compared with triple-negative breast cancers. Luminal tumors that are responsive to hormonal therapy are particularly associated with a favorable prognosis. Nonetheless, the absolute...

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Autores principales: Coillard, Lucie, Guaddachi, Frédéric, Ralu, Maëlle, Brabencova, Eva, Garbar, Christian, Bensussan, Armand, Le Bras, Morgane, Lehmann-Che, Jacqueline, Jauliac, Sébastien
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9280138/
https://www.ncbi.nlm.nih.gov/pubmed/35847954
http://dx.doi.org/10.3389/fonc.2022.804868
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author Coillard, Lucie
Guaddachi, Frédéric
Ralu, Maëlle
Brabencova, Eva
Garbar, Christian
Bensussan, Armand
Le Bras, Morgane
Lehmann-Che, Jacqueline
Jauliac, Sébastien
author_facet Coillard, Lucie
Guaddachi, Frédéric
Ralu, Maëlle
Brabencova, Eva
Garbar, Christian
Bensussan, Armand
Le Bras, Morgane
Lehmann-Che, Jacqueline
Jauliac, Sébastien
author_sort Coillard, Lucie
collection PubMed
description Luminal breast cancers represent 70% of newly diagnosed breast cancers per annum and have a relatively good prognosis compared with triple-negative breast cancers. Luminal tumors that are responsive to hormonal therapy are particularly associated with a favorable prognosis. Nonetheless, the absolute number of metastatic relapses in luminal cancers is larger than in triple-negative breast cancers. A better understanding of the biology of luminal cancers, control of metastases formation, and identification of predictive markers of their evolution are therefore still necessary. In this context, we previously disclosed the key role of NFAT3 in regulating luminal breast cancer invasion. We have now identified a specific inhibitory region, in the C-terminal part of NFAT3, required for the inhibition of invasion of the human luminal breast cancer cell line T-47D. Indeed, we showed that this 85 amino acid C-terminal region acts as a dominant negative form of NFAT3 and that its overexpression in the T-47D cell line led to increased cell invasion. Mechanistically, we have revealed that this region of NFAT3 interacts with the small Ras GTPase RERG (RAS like estrogen regulated growth inhibitor) and shown that RERG expression is required for NFAT3 to impede T-47D cell invasion. We have validated the association of NFAT3 with RERG in human luminal breast cancer tissues. We have shown an increase of the quantity of the NFAT3/RERG complexes in patients without axillary lymph node colonization and therefore proposed that the detection of this complex may be a non-invasive marker of axillary lymph node colonization.
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spelling pubmed-92801382022-07-15 The NFAT3/RERG Complex in Luminal Breast Cancers Is Required to Inhibit Cell Invasion and May Be Correlated With an Absence of Axillary Lymph Nodes Colonization Coillard, Lucie Guaddachi, Frédéric Ralu, Maëlle Brabencova, Eva Garbar, Christian Bensussan, Armand Le Bras, Morgane Lehmann-Che, Jacqueline Jauliac, Sébastien Front Oncol Oncology Luminal breast cancers represent 70% of newly diagnosed breast cancers per annum and have a relatively good prognosis compared with triple-negative breast cancers. Luminal tumors that are responsive to hormonal therapy are particularly associated with a favorable prognosis. Nonetheless, the absolute number of metastatic relapses in luminal cancers is larger than in triple-negative breast cancers. A better understanding of the biology of luminal cancers, control of metastases formation, and identification of predictive markers of their evolution are therefore still necessary. In this context, we previously disclosed the key role of NFAT3 in regulating luminal breast cancer invasion. We have now identified a specific inhibitory region, in the C-terminal part of NFAT3, required for the inhibition of invasion of the human luminal breast cancer cell line T-47D. Indeed, we showed that this 85 amino acid C-terminal region acts as a dominant negative form of NFAT3 and that its overexpression in the T-47D cell line led to increased cell invasion. Mechanistically, we have revealed that this region of NFAT3 interacts with the small Ras GTPase RERG (RAS like estrogen regulated growth inhibitor) and shown that RERG expression is required for NFAT3 to impede T-47D cell invasion. We have validated the association of NFAT3 with RERG in human luminal breast cancer tissues. We have shown an increase of the quantity of the NFAT3/RERG complexes in patients without axillary lymph node colonization and therefore proposed that the detection of this complex may be a non-invasive marker of axillary lymph node colonization. Frontiers Media S.A. 2022-06-30 /pmc/articles/PMC9280138/ /pubmed/35847954 http://dx.doi.org/10.3389/fonc.2022.804868 Text en Copyright © 2022 Coillard, Guaddachi, Ralu, Brabencova, Garbar, Bensussan, Le Bras, Lehmann-Che and Jauliac https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Coillard, Lucie
Guaddachi, Frédéric
Ralu, Maëlle
Brabencova, Eva
Garbar, Christian
Bensussan, Armand
Le Bras, Morgane
Lehmann-Che, Jacqueline
Jauliac, Sébastien
The NFAT3/RERG Complex in Luminal Breast Cancers Is Required to Inhibit Cell Invasion and May Be Correlated With an Absence of Axillary Lymph Nodes Colonization
title The NFAT3/RERG Complex in Luminal Breast Cancers Is Required to Inhibit Cell Invasion and May Be Correlated With an Absence of Axillary Lymph Nodes Colonization
title_full The NFAT3/RERG Complex in Luminal Breast Cancers Is Required to Inhibit Cell Invasion and May Be Correlated With an Absence of Axillary Lymph Nodes Colonization
title_fullStr The NFAT3/RERG Complex in Luminal Breast Cancers Is Required to Inhibit Cell Invasion and May Be Correlated With an Absence of Axillary Lymph Nodes Colonization
title_full_unstemmed The NFAT3/RERG Complex in Luminal Breast Cancers Is Required to Inhibit Cell Invasion and May Be Correlated With an Absence of Axillary Lymph Nodes Colonization
title_short The NFAT3/RERG Complex in Luminal Breast Cancers Is Required to Inhibit Cell Invasion and May Be Correlated With an Absence of Axillary Lymph Nodes Colonization
title_sort nfat3/rerg complex in luminal breast cancers is required to inhibit cell invasion and may be correlated with an absence of axillary lymph nodes colonization
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9280138/
https://www.ncbi.nlm.nih.gov/pubmed/35847954
http://dx.doi.org/10.3389/fonc.2022.804868
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