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Article ; Online: Zinc Favors Triple-Negative Breast Cancer's Microenvironment Modulation and Cell Plasticity.

Vogel-González, Marina / Musa-Afaneh, Dunia / Rivera Gil, Pilar / Vicente, Rubén

International journal of molecular sciences

2021 Volume 22, Issue 17

Abstract: Triple-negative breast cancer (TNBC) tends to metastasize to the brain, a step that worsens the patient's prognosis. The specific hallmarks that determine successful metastasis are motility and invasion, microenvironment modulation, plasticity, and ... ...

Abstract	Triple-negative breast cancer (TNBC) tends to metastasize to the brain, a step that worsens the patient's prognosis. The specific hallmarks that determine successful metastasis are motility and invasion, microenvironment modulation, plasticity, and colonization. Zinc, an essential trace element, has been shown to be involved in all of these processes. In this work, we focus our attention on the potential role of zinc during TNBC metastasis. We used MDA-MB-BrM2 (BrM2) cells, a brain metastasis model derived from the parental TNBC cell line MDA-MB-231. Our studies show that BrM2 cells had double the zinc content of MDA-MB-231 cells. Moreover, exploring different metastatic hallmarks, we found that the zinc concentration is especially important in the microenvironment modulation of brain metastatic cells, enhancing the expression of SerpinB2. Furthermore, we show that zinc promotes the tumorigenic capacity of breast cancer stem cells. In addition, by causing a disturbance in MDA-MB-231 zinc homeostasis by overexpressing the Zip4 transporter, we were able to increase tumorigenicity. Nevertheless, this strategy did not completely recapitulate the BrM2 metastatic phenotype. Altogether, our work suggests that zinc plays an important role in the transformative steps that tumoral cells take to acquire tumorigenic potential and niche specificity.
MeSH term(s)	Cation Transport Proteins/genetics ; Cation Transport Proteins/metabolism ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Humans ; Plasminogen Activator Inhibitor 2/genetics ; Plasminogen Activator Inhibitor 2/metabolism ; Triple Negative Breast Neoplasms/metabolism ; Tumor Microenvironment ; Zinc/metabolism
Chemical Substances	Cation Transport Proteins ; Plasminogen Activator Inhibitor 2 ; SLC39A4 protein, human ; Zinc (J41CSQ7QDS)
Language	English
Publishing date	2021-08-25
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms22179188
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Human genetic adaptation related to cellular zinc homeostasis.

Roca-Umbert, Ana / Garcia-Calleja, Jorge / Vogel-González, Marina / Fierro-Villegas, Alejandro / Ill-Raga, Gerard / Herrera-Fernández, Víctor / Bosnjak, Anja / Muntané, Gerard / Gutiérrez, Esteban / Campelo, Felix / Vicente, Rubén / Bosch, Elena

PLoS genetics

2023 Volume 19, Issue 9, Page(s) e1010950

Abstract: SLC30A9 encodes a ubiquitously zinc transporter (ZnT9) and has been consistently suggested as a candidate for positive selection in humans. However, no direct adaptive molecular phenotype has been demonstrated. Our results provide evidence for ... ...

Abstract	SLC30A9 encodes a ubiquitously zinc transporter (ZnT9) and has been consistently suggested as a candidate for positive selection in humans. However, no direct adaptive molecular phenotype has been demonstrated. Our results provide evidence for directional selection operating in two major complementary haplotypes in Africa and East Asia. These haplotypes are associated with differential gene expression but also differ in the Met50Val substitution (rs1047626) in ZnT9, which we show is found in homozygosis in the Denisovan genome and displays accompanying signatures suggestive of archaic introgression. Although we found no significant differences in systemic zinc content between individuals with different rs1047626 genotypes, we demonstrate that the expression of the derived isoform (ZnT9 50Val) in HEK293 cells shows a gain of function when compared with the ancestral (ZnT9 50Met) variant. Notably, the ZnT9 50Val variant was found associated with differences in zinc handling by the mitochondria and endoplasmic reticulum, with an impact on mitochondrial metabolism. Given the essential role of the mitochondria in skeletal muscle and since the derived allele at rs1047626 is known to be associated with greater susceptibility to several neuropsychiatric traits, we propose that adaptation to cold may have driven this selection event, while also impacting predisposition to neuropsychiatric disorders in modern humans.
MeSH term(s)	Animals ; Humans ; HEK293 Cells ; Hominidae/genetics ; Homeostasis/genetics ; Zinc ; Human Genetics ; Selection, Genetic ; Haplotypes ; Genome, Human
Chemical Substances	Zinc (J41CSQ7QDS)
Language	English
Publishing date	2023-09-25
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2186725-2
ISSN	1553-7404 ; 1553-7390
ISSN (online)	1553-7404
ISSN	1553-7390
DOI	10.1371/journal.pgen.1010950
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Article ; Online: The mechanosensitive Piezo1 channel controls endosome trafficking for an efficient cytokinetic abscission.

Carrillo-Garcia, Julia / Herrera-Fernández, Víctor / Serra, Selma A / Rubio-Moscardo, Fanny / Vogel-Gonzalez, Marina / Doñate-Macian, Pablo / Hevia, Covadonga F / Pujades, Cristina / Valverde, Miguel A

Science advances

2021 Volume 7, Issue 44, Page(s) eabi7785

Abstract: Mechanical forces are exerted throughout cytokinesis, the final step of cell division. Yet, how forces are transduced and affect the signaling dynamics of cytokinetic proteins remains poorly characterized. We now show that the mechanosensitive Piezo1 ... ...

Abstract	Mechanical forces are exerted throughout cytokinesis, the final step of cell division. Yet, how forces are transduced and affect the signaling dynamics of cytokinetic proteins remains poorly characterized. We now show that the mechanosensitive Piezo1 channel is activated at the intercellular bridge (ICB) connecting daughter cells to regulate abscission. Inhibition of Piezo1 caused multinucleation both in vitro and in vivo. Piezo1 positioning at the ICB during cytokinesis depends on Pacsin3. Pharmacological and genetic inhibition of Piezo1 or Pacsin3 resulted in mislocation of Rab11-family-interacting protein 3 (Rab11-FIP3) endosomes, apoptosis-linked gene 2-interacting protein X (ALIX), and endosomal sorting complex required for transport III (ESCRT-III). Furthermore, we identified FIP3 as the link between Piezo1-generated Ca
Language	English
Publishing date	2021-10-29
Publishing country	United States
Document type	Journal Article
ZDB-ID	2810933-8
ISSN	2375-2548 ; 2375-2548
ISSN (online)	2375-2548
ISSN	2375-2548
DOI	10.1126/sciadv.abi7785
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Article ; Online: New hPSC-based human models to study pediatric Acute Megakaryoblastic Leukemia harboring the fusion oncogene RBM15-MKL1.

Ayllón, Verónica / Vogel-González, Marina / González-Pozas, Federico / Domingo-Reinés, Joan / Montes, Rosa / Morales-Cacho, Lucía / Ramos-Mejía, Verónica

Stem cell research

2017 Volume 19, Page(s) 1–5

Abstract: Pediatric Acute Megakaryoblastic Leukemia not associated to Down Syndrome (non-DS AMKL) is a rare disease with a dismal prognosis. Around 15% of patients carry the chromosomal translocation t(1;22) that originates the fusion oncogene RBM15-MKL1, which is ...

Abstract	Pediatric Acute Megakaryoblastic Leukemia not associated to Down Syndrome (non-DS AMKL) is a rare disease with a dismal prognosis. Around 15% of patients carry the chromosomal translocation t(1;22) that originates the fusion oncogene RBM15-MKL1, which is linked to an earlier disease onset (median of 6months of age) and arises in utero. Here we report the generation of two hPSC cell lines constitutively expressing the oncogene RBM15-MKL1, resulting in an increased expression of known RBM15-MKL1 gene targets. These cell lines represent new disease models of pediatric AMKL to study the impact of the RBM15-MKL1 oncogene on human embryonic hematopoietic development.
MeSH term(s)	Biomarkers/metabolism ; Cell Line ; Child ; Genetic Vectors/genetics ; Genetic Vectors/metabolism ; Humans ; Leukemia, Megakaryoblastic, Acute/metabolism ; Leukemia, Megakaryoblastic, Acute/pathology ; Models, Biological ; Oncogene Proteins, Fusion/genetics ; Oncogene Proteins, Fusion/metabolism ; Pluripotent Stem Cells/cytology ; Pluripotent Stem Cells/metabolism ; Transcription Factors/genetics ; Transcription Factors/metabolism
Chemical Substances	Biomarkers ; OTT-MAL fusion protein, human ; Oncogene Proteins, Fusion ; Transcription Factors
Language	English
Publishing date	2017-03
Publishing country	England
Document type	Journal Article
ISSN	1876-7753
ISSN (online)	1876-7753
DOI	10.1016/j.scr.2016.12.019
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Low Zinc Levels at Admission Associates with Poor Clinical Outcomes in SARS-CoV-2 Infection.

Vogel-González, Marina / Talló-Parra, Marc / Herrera-Fernández, Víctor / Pérez-Vilaró, Gemma / Chillón, Miguel / Nogués, Xavier / Gómez-Zorrilla, Silvia / López-Montesinos, Inmaculada / Arnau-Barrés, Isabel / Sorli-Redó, Maria Luisa / Horcajada, Juan Pablo / García-Giralt, Natalia / Pascual, Julio / Díez, Juana / Vicente, Rubén / Güerri-Fernández, Robert

Nutrients

2021 Volume 13, Issue 2

Abstract: Background: Zinc is an essential micronutrient that impacts host-pathogen interplay at infection. Zinc balances immune responses, and also has a proven direct antiviral action against some viruses. Importantly, zinc deficiency (ZD) is a common condition ...

Abstract	Background: Zinc is an essential micronutrient that impacts host-pathogen interplay at infection. Zinc balances immune responses, and also has a proven direct antiviral action against some viruses. Importantly, zinc deficiency (ZD) is a common condition in elderly and individuals with chronic diseases, two groups with an increased risk for severe severe coronavirus disease 2019 (COVID-19) outcomes. We hypothesize that serum zinc content (SZC) influences COVID-19 disease progression, and thus might represent a useful biomarker. Methods: We ran an observational cohort study with 249 COVID-19 patients admitted in Hospital del Mar. We have studied COVID-19 severity and progression attending to SZC at admission. In parallel, we have studied severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) replication in the Vero E6 cell line modifying zinc concentrations. Findings: Our study demonstrates a correlation between serum zinc levels and COVID-19 outcome. Serum zinc levels lower than 50 µg/dL at admission correlated with worse clinical presentation, longer time to reach stability, and higher mortality. Our in vitro results indicate that low zinc levels favor viral expansion in SARS-CoV-2 infected cells. Interpretation: Low SZC is a risk factor that determines COVID-19 outcome. We encourage performing randomized clinical trials to study zinc supplementation as potential prophylaxis and treatment with people at risk of zinc deficiency.
MeSH term(s)	Aged ; Animals ; COVID-19/blood ; COVID-19/pathology ; Cell Survival ; Chlorocebus aethiops ; Cohort Studies ; Female ; Humans ; Male ; Middle Aged ; SARS-CoV-2 ; Vero Cells ; Zinc/administration & dosage ; Zinc/blood ; Zinc/pharmacology
Chemical Substances	Zinc (J41CSQ7QDS)
Language	English
Publishing date	2021-02-09
Publishing country	Switzerland
Document type	Journal Article ; Observational Study
ZDB-ID	2518386-2
ISSN	2072-6643 ; 2072-6643
ISSN (online)	2072-6643
ISSN	2072-6643
DOI	10.3390/nu13020562
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Article ; Online: Low Zinc Levels at Clinical Admission Associates with Poor Outcomes in COVID-19

Vogel-González, Marina / Talló-Parra, Marc / Herrera-Fernández, Víctor / Pérez-Vilaró, Gemma / Chillón, Miguel / Nogués, Xavier / Gómez-Zorrilla, Silvia / López-Montesinos, Inmaculada / Villar, Judit / Sorlí-Redó, Luisa / Horcajada, Juan Pablo / García-Giralt, Natalia / Pascual, Julio / Díez, Juana / Vicente, Rubén / Güerri-Fernández, Robert

SSRN Electronic Journal ; ISSN 1556-5068

2020

Keywords	covid19
Language	English
Publisher	Elsevier BV
Publishing country	us
Document type	Article ; Online
DOI	10.2139/ssrn.3696880
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Piezo2 channel regulates RhoA and actin cytoskeleton to promote cell mechanobiological responses.

Pardo-Pastor, Carlos / Rubio-Moscardo, Fanny / Vogel-González, Marina / Serra, Selma A / Afthinos, Alexandros / Mrkonjic, Sanela / Destaing, Olivier / Abenza, Juan F / Fernández-Fernández, José M / Trepat, Xavier / Albiges-Rizo, Corinne / Konstantopoulos, Konstantinos / Valverde, Miguel A

Proceedings of the National Academy of Sciences of the United States of America

2018 Volume 115, Issue 8, Page(s) 1925–1930

Abstract: Actin polymerization and assembly into stress fibers (SFs) is central to many cellular processes. However, how SFs form in response to the mechanical interaction of cells with their environment is not fully understood. Here we have identified Piezo2 ... ...

Abstract	Actin polymerization and assembly into stress fibers (SFs) is central to many cellular processes. However, how SFs form in response to the mechanical interaction of cells with their environment is not fully understood. Here we have identified Piezo2 mechanosensitive cationic channel as a transducer of environmental physical cues into mechanobiological responses. Piezo2 is needed by brain metastatic cells from breast cancer (MDA-MB-231-BrM2) to probe their physical environment as they anchor and pull on their surroundings or when confronted with confined migration through narrow pores. Piezo2-mediated Ca
MeSH term(s)	Actin Cytoskeleton/genetics ; Actin Cytoskeleton/metabolism ; Calcium/metabolism ; Cell Line, Tumor ; Cell Movement ; Gene Expression Regulation, Neoplastic ; Gene Knockdown Techniques ; HEK293 Cells ; Humans ; Ion Channels/genetics ; Ion Channels/metabolism ; Mechanotransduction, Cellular/physiology ; rhoA GTP-Binding Protein/genetics ; rhoA GTP-Binding Protein/metabolism
Chemical Substances	Ion Channels ; PIEZO2 protein, human ; RHOA protein, human (124671-05-2) ; rhoA GTP-Binding Protein (EC 3.6.5.2) ; Calcium (SY7Q814VUP)
Language	English
Publishing date	2018-02-05
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.1718177115
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Article: Higgs physics at the CLIC electron-positron linear collider.

Abramowicz, H / Abusleme, A / Afanaciev, K / Alipour Tehrani, N / Balázs, C / Benhammou, Y / Benoit, M / Bilki, B / Blaising, J-J / Boland, M J / Boronat, M / Borysov, O / Božović-Jelisavčić, I / Buckland, M / Bugiel, S / Burrows, P N / Charles, T K / Daniluk, W / Dannheim, D /

Dasgupta, R / Demarteau, M / Díaz Gutierrez, M A / Eigen, G / Elsener, K / Felzmann, U / Firlej, M / Firu, E / Fiutowski, T / Fuster, J / Gabriel, M / Gaede, F / García, I / Ghenescu, V / Goldstein, J / Green, S / Grefe, C / Hauschild, M / Hawkes, C / Hynds, D / Idzik, M / Kačarević, G / Kalinowski, J / Kananov, S / Klempt, W / Kopec, M / Krawczyk, M / Krupa, B / Kucharczyk, M / Kulis, S / Laštovička, T / Lesiak, T / Levy, A / Levy, I / Linssen, L / Lukić, S / Maier, A A / Makarenko, V / Marshall, J S / Martin, V J / Mei, K / Milutinović-Dumbelović, G / Moroń, J / Moszczyński, A / Moya, D / Münker, R M / Münnich, A / Neagu, A T / Nikiforou, N / Nikolopoulos, K / Nürnberg, A / Pandurović, M / Pawlik, B / Perez Codina, E / Peric, I / Petric, M / Pitters, F / Poss, S G / Preda, T / Protopopescu, D / Rassool, R / Redford, S / Repond, J / Robson, A / Roloff, P / Ros, E / Rosenblat, O / Ruiz-Jimeno, A / Sailer, A / Schlatter, D / Schulte, D / Shumeiko, N / Sicking, E / Simon, F / Simoniello, R / Sopicki, P / Stapnes, S / Ström, R / Strube, J / Świentek, K P / Szalay, M / Tesař, M / Thomson, M A / Trenado, J / Uggerhøj, U I / van der Kolk, N / van der Kraaij, E / Vicente Barreto Pinto, M / Vila, I / Vogel Gonzalez, M / Vos, M / Vossebeld, J / Watson, M / Watson, N / Weber, M A / Weerts, H / Wells, J D / Weuste, L / Winter, A / Wojtoń, T / Xia, L / Xu, B / Żarnecki, A F / Zawiejski, L / Zgura, I-S

The European physical journal. C, Particles and fields

2017 Volume 77, Issue 7, Page(s) 475

Abstract: The Compact Linear Collider (CLIC) is an option for a future [Formula: see text] collider operating at centre-of-mass energies up to [Formula: see text], providing sensitivity to a wide range of new physics phenomena and precision physics measurements at ...

Abstract	The Compact Linear Collider (CLIC) is an option for a future [Formula: see text] collider operating at centre-of-mass energies up to [Formula: see text], providing sensitivity to a wide range of new physics phenomena and precision physics measurements at the energy frontier. This paper is the first comprehensive presentation of the Higgs physics reach of CLIC operating at three energy stages: [Formula: see text], 1.4 and [Formula: see text]. The initial stage of operation allows the study of Higgs boson production in Higgsstrahlung ([Formula: see text]) and [Formula: see text]-fusion ([Formula: see text]), resulting in precise measurements of the production cross sections, the Higgs total decay width [Formula: see text], and model-independent determinations of the Higgs couplings. Operation at [Formula: see text] provides high-statistics samples of Higgs bosons produced through [Formula: see text]-fusion, enabling tight constraints on the Higgs boson couplings. Studies of the rarer processes [Formula: see text] and [Formula: see text] allow measurements of the top Yukawa coupling and the Higgs boson self-coupling. This paper presents detailed studies of the precision achievable with Higgs measurements at CLIC and describes the interpretation of these measurements in a global fit.
Language	English
Publishing date	2017-07-17
Publishing country	France
Document type	Journal Article
ZDB-ID	1459069-4
ISSN	1434-6052 ; 1434-6044
ISSN (online)	1434-6052
ISSN	1434-6044
DOI	10.1140/epjc/s10052-017-4968-5
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Article ; Online: Zinc Favors Triple-Negative Breast Cancer's Microenvironment Modulation and Cell Plasticity.

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Article ; Online: Human genetic adaptation related to cellular zinc homeostasis.

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Article ; Online: The mechanosensitive Piezo1 channel controls endosome trafficking for an efficient cytokinetic abscission.

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Article ; Online: New hPSC-based human models to study pediatric Acute Megakaryoblastic Leukemia harboring the fusion oncogene RBM15-MKL1.

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Article ; Online: Low Zinc Levels at Admission Associates with Poor Clinical Outcomes in SARS-CoV-2 Infection.

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Article ; Online: Low Zinc Levels at Clinical Admission Associates with Poor Outcomes in COVID-19

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Article ; Online: Piezo2 channel regulates RhoA and actin cytoskeleton to promote cell mechanobiological responses.

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Article: Higgs physics at the CLIC electron-positron linear collider.

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