Zinc Status Impacts the Epidermal Growth Factor Receptor and Downstream Protein Expression in A549 Cells

Zinc has been suggested to play a role in carcinogenesis and tumor progression. Serum zinc levels of lung cancer patients are for example lower than in healthy individuals. The activation and expression of the epidermal growth factor receptor (EGFR), which plays a role in tumor biology, are presumab...

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Main Authors: Emily Scheiermann, Mary-Ann Puppa, Lothar Rink, Inga Wessels
Format: Article
Language:English
Published: MDPI AG 2022-02-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/23/4/2270
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author Emily Scheiermann
Mary-Ann Puppa
Lothar Rink
Inga Wessels
author_facet Emily Scheiermann
Mary-Ann Puppa
Lothar Rink
Inga Wessels
author_sort Emily Scheiermann
collection DOAJ
description Zinc has been suggested to play a role in carcinogenesis and tumor progression. Serum zinc levels of lung cancer patients are for example lower than in healthy individuals. The activation and expression of the epidermal growth factor receptor (EGFR), which plays a role in tumor biology, are presumably influenced by zinc. EGFR activation influences cell adhesion and immune escape. This study provides insights into the impacts of zinc on the EGFR activation and expression of downstream proteins such as E-cadherin and PD-L1 in the alveolar carcinoma cell line A549. To model chronic changes in zinc homeostasis, A549 cells were cultured in media with different zinc contents. EGFR surface expression of unstimulated and stimulated A549 cells was determined by flow cytometry. EGFR phosphorylation as well as the protein expression of E-cadherin and PD-L1 were analyzed by Western blot. In our hands, chronic zinc deficiency led to increased EGFR surface expression, decreased E-cadherin protein expression and increased PD-L1 protein expression. Zinc supplementation decreased EGFR surface expression and PD-L1 protein expression. In summary, zinc-deficient A549 cells may display a more malignant phenotype. Thus, future clinical research should further focus on the possible benefits of restoring disturbed zinc homeostasis, especially in lung cancer patients.
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spelling doaj.art-de3f88fde9754b73b9c2dcbf2bd1b0682023-11-23T20:22:42ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-02-01234227010.3390/ijms23042270Zinc Status Impacts the Epidermal Growth Factor Receptor and Downstream Protein Expression in A549 CellsEmily Scheiermann0Mary-Ann Puppa1Lothar Rink2Inga Wessels3Institute of Immunology, Medical Faculty, RWTH Aachen University, Pauwelsstraße 30, D-52074 Aachen, GermanyInstitute of Immunology, Medical Faculty, RWTH Aachen University, Pauwelsstraße 30, D-52074 Aachen, GermanyInstitute of Immunology, Medical Faculty, RWTH Aachen University, Pauwelsstraße 30, D-52074 Aachen, GermanyInstitute of Immunology, Medical Faculty, RWTH Aachen University, Pauwelsstraße 30, D-52074 Aachen, GermanyZinc has been suggested to play a role in carcinogenesis and tumor progression. Serum zinc levels of lung cancer patients are for example lower than in healthy individuals. The activation and expression of the epidermal growth factor receptor (EGFR), which plays a role in tumor biology, are presumably influenced by zinc. EGFR activation influences cell adhesion and immune escape. This study provides insights into the impacts of zinc on the EGFR activation and expression of downstream proteins such as E-cadherin and PD-L1 in the alveolar carcinoma cell line A549. To model chronic changes in zinc homeostasis, A549 cells were cultured in media with different zinc contents. EGFR surface expression of unstimulated and stimulated A549 cells was determined by flow cytometry. EGFR phosphorylation as well as the protein expression of E-cadherin and PD-L1 were analyzed by Western blot. In our hands, chronic zinc deficiency led to increased EGFR surface expression, decreased E-cadherin protein expression and increased PD-L1 protein expression. Zinc supplementation decreased EGFR surface expression and PD-L1 protein expression. In summary, zinc-deficient A549 cells may display a more malignant phenotype. Thus, future clinical research should further focus on the possible benefits of restoring disturbed zinc homeostasis, especially in lung cancer patients.https://www.mdpi.com/1422-0067/23/4/2270zincEGFRlung cancerE-cadherinPD-L1
spellingShingle Emily Scheiermann
Mary-Ann Puppa
Lothar Rink
Inga Wessels
Zinc Status Impacts the Epidermal Growth Factor Receptor and Downstream Protein Expression in A549 Cells
International Journal of Molecular Sciences
zinc
EGFR
lung cancer
E-cadherin
PD-L1
title Zinc Status Impacts the Epidermal Growth Factor Receptor and Downstream Protein Expression in A549 Cells
title_full Zinc Status Impacts the Epidermal Growth Factor Receptor and Downstream Protein Expression in A549 Cells
title_fullStr Zinc Status Impacts the Epidermal Growth Factor Receptor and Downstream Protein Expression in A549 Cells
title_full_unstemmed Zinc Status Impacts the Epidermal Growth Factor Receptor and Downstream Protein Expression in A549 Cells
title_short Zinc Status Impacts the Epidermal Growth Factor Receptor and Downstream Protein Expression in A549 Cells
title_sort zinc status impacts the epidermal growth factor receptor and downstream protein expression in a549 cells
topic zinc
EGFR
lung cancer
E-cadherin
PD-L1
url https://www.mdpi.com/1422-0067/23/4/2270
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AT lotharrink zincstatusimpactstheepidermalgrowthfactorreceptoranddownstreamproteinexpressionina549cells
AT ingawessels zincstatusimpactstheepidermalgrowthfactorreceptoranddownstreamproteinexpressionina549cells