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Opposing Effects of Chelidonine on Tyrosine and Serine Phosphorylation of STAT3 in Human Uveal Melanoma Cells

STAT3 is a transcription factor that regulates various cellular processes with oncogenic potential, thereby promoting tumorigenesis when activated uncontrolled. STAT3 activation is mediated by its tyrosine phosphorylation, triggering dimerization and nuclear translocation. STAT3 also contains a seri...

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Autores principales: Csomós, István, Nagy, Péter, Filep, Csenge, Rebenku, István, Nizsalóczki, Enikő, Kovács, Tamás, Vámosi, György, Mátyus, László, Bodnár, Andrea
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8658041/
https://www.ncbi.nlm.nih.gov/pubmed/34884773
http://dx.doi.org/10.3390/ijms222312974
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author Csomós, István
Nagy, Péter
Filep, Csenge
Rebenku, István
Nizsalóczki, Enikő
Kovács, Tamás
Vámosi, György
Mátyus, László
Bodnár, Andrea
author_facet Csomós, István
Nagy, Péter
Filep, Csenge
Rebenku, István
Nizsalóczki, Enikő
Kovács, Tamás
Vámosi, György
Mátyus, László
Bodnár, Andrea
author_sort Csomós, István
collection PubMed
description STAT3 is a transcription factor that regulates various cellular processes with oncogenic potential, thereby promoting tumorigenesis when activated uncontrolled. STAT3 activation is mediated by its tyrosine phosphorylation, triggering dimerization and nuclear translocation. STAT3 also contains a serine phosphorylation site, with a postulated regulatory role in STAT3 activation and G2/M transition. Interleukin-6, a major activator of STAT3, is present in elevated concentrations in uveal melanomas, suggesting contribution of dysregulated STAT3 activation to their pathogenesis. Here, we studied the impact of chelidonine on STAT3 signaling in human uveal melanoma cells. Chelidonine, an alkaloid isolated from Chelidonium majus, disrupts microtubules, causes mitotic arrest and provokes cell death in numerous tumor cells. According to our flow cytometry and confocal microscopy data, chelidonine abrogated IL-6-induced activation and nuclear translocation, but amplified constitutive serine phosphorylation of STAT3. Both effects were restricted to a fraction of cells only, in an all-or-none fashion. A partial overlap could be observed between the affected subpopulations; however, no direct connection could be proven. This study is the first proof on a cell-by-cell basis for the opposing effects of a microtubule-targeting agent on the two types of STAT3 phosphorylation.
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spelling pubmed-86580412021-12-10 Opposing Effects of Chelidonine on Tyrosine and Serine Phosphorylation of STAT3 in Human Uveal Melanoma Cells Csomós, István Nagy, Péter Filep, Csenge Rebenku, István Nizsalóczki, Enikő Kovács, Tamás Vámosi, György Mátyus, László Bodnár, Andrea Int J Mol Sci Article STAT3 is a transcription factor that regulates various cellular processes with oncogenic potential, thereby promoting tumorigenesis when activated uncontrolled. STAT3 activation is mediated by its tyrosine phosphorylation, triggering dimerization and nuclear translocation. STAT3 also contains a serine phosphorylation site, with a postulated regulatory role in STAT3 activation and G2/M transition. Interleukin-6, a major activator of STAT3, is present in elevated concentrations in uveal melanomas, suggesting contribution of dysregulated STAT3 activation to their pathogenesis. Here, we studied the impact of chelidonine on STAT3 signaling in human uveal melanoma cells. Chelidonine, an alkaloid isolated from Chelidonium majus, disrupts microtubules, causes mitotic arrest and provokes cell death in numerous tumor cells. According to our flow cytometry and confocal microscopy data, chelidonine abrogated IL-6-induced activation and nuclear translocation, but amplified constitutive serine phosphorylation of STAT3. Both effects were restricted to a fraction of cells only, in an all-or-none fashion. A partial overlap could be observed between the affected subpopulations; however, no direct connection could be proven. This study is the first proof on a cell-by-cell basis for the opposing effects of a microtubule-targeting agent on the two types of STAT3 phosphorylation. MDPI 2021-11-30 /pmc/articles/PMC8658041/ /pubmed/34884773 http://dx.doi.org/10.3390/ijms222312974 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
Csomós, István
Nagy, Péter
Filep, Csenge
Rebenku, István
Nizsalóczki, Enikő
Kovács, Tamás
Vámosi, György
Mátyus, László
Bodnár, Andrea
Opposing Effects of Chelidonine on Tyrosine and Serine Phosphorylation of STAT3 in Human Uveal Melanoma Cells
title Opposing Effects of Chelidonine on Tyrosine and Serine Phosphorylation of STAT3 in Human Uveal Melanoma Cells
title_full Opposing Effects of Chelidonine on Tyrosine and Serine Phosphorylation of STAT3 in Human Uveal Melanoma Cells
title_fullStr Opposing Effects of Chelidonine on Tyrosine and Serine Phosphorylation of STAT3 in Human Uveal Melanoma Cells
title_full_unstemmed Opposing Effects of Chelidonine on Tyrosine and Serine Phosphorylation of STAT3 in Human Uveal Melanoma Cells
title_short Opposing Effects of Chelidonine on Tyrosine and Serine Phosphorylation of STAT3 in Human Uveal Melanoma Cells
title_sort opposing effects of chelidonine on tyrosine and serine phosphorylation of stat3 in human uveal melanoma cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8658041/
https://www.ncbi.nlm.nih.gov/pubmed/34884773
http://dx.doi.org/10.3390/ijms222312974
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