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Endoplasmic Reticulum Adaptation and Autophagic Competence Shape Response to Fluid Shear Stress in T24 Bladder Cancer Cells

Accumulation of xenobiotics and waste metabolites in the urinary bladder is constantly accompanied by shear stress originating from the movement of the luminal fluids. Hence, both chemical and physical cues constantly modulate the cellular response in health and disease. In line, bladder cells have...

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Autores principales: Del Favero, Giorgia, Zeugswetter, Michael, Kiss, Endre, Marko, Doris
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8126838/
https://www.ncbi.nlm.nih.gov/pubmed/34012396
http://dx.doi.org/10.3389/fphar.2021.647350
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author Del Favero, Giorgia
Zeugswetter, Michael
Kiss, Endre
Marko, Doris
author_facet Del Favero, Giorgia
Zeugswetter, Michael
Kiss, Endre
Marko, Doris
author_sort Del Favero, Giorgia
collection PubMed
description Accumulation of xenobiotics and waste metabolites in the urinary bladder is constantly accompanied by shear stress originating from the movement of the luminal fluids. Hence, both chemical and physical cues constantly modulate the cellular response in health and disease. In line, bladder cells have to maintain elevated mechanosensory competence together with chemical stress response adaptation potential. However, much of the molecular mechanisms sustaining this plasticity is currently unknown. Taking this as a starting point, we investigated the response of T24 urinary bladder cancer cells to shear stress comparing morphology to functional performance. T24 cells responded to the shear stress protocol (flow speed of 0.03 ml/min, 3 h) by significantly increasing their surface area. When exposed to deoxynivalenol-3-sulfate (DON-3-Sulf), bladder cells increased this response in a concentration-dependent manner (0.1–1 µM). DON-3-Sulf is a urinary metabolite of a very common food contaminant mycotoxin (deoxynivalenol, DON) and was already described to enhance proliferation of cancer cells. Incubation with DON-3-Sulf also caused the enlargement of the endoplasmic reticulum (ER), decreased the lysosomal movement, and increased the formation of actin stress fibers. Similar remodeling of the endoplasmic reticulum and area spread after shear stress were observed upon incubation with the autophagy activator rapamycin (1–100 nM). Performance of experiments in the presence of chloroquine (chloroquine, 30 μM) further contributed to shed light on the mechanistic link between adaptation to the biomechanical stimulation and ER stress response. At the molecular level, we observed that ER reshaping was linked to actin organization, with the two components mutually regulating each other. Indeed, we identified in the ER stress–cytoskeletal rearrangement an important axis defining the physical/chemical response potential of bladder cells and created a workflow for further investigation of urinary metabolites, food constituents, and contaminants, as well as for pharmacological profiling.
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spelling pubmed-81268382021-05-18 Endoplasmic Reticulum Adaptation and Autophagic Competence Shape Response to Fluid Shear Stress in T24 Bladder Cancer Cells Del Favero, Giorgia Zeugswetter, Michael Kiss, Endre Marko, Doris Front Pharmacol Pharmacology Accumulation of xenobiotics and waste metabolites in the urinary bladder is constantly accompanied by shear stress originating from the movement of the luminal fluids. Hence, both chemical and physical cues constantly modulate the cellular response in health and disease. In line, bladder cells have to maintain elevated mechanosensory competence together with chemical stress response adaptation potential. However, much of the molecular mechanisms sustaining this plasticity is currently unknown. Taking this as a starting point, we investigated the response of T24 urinary bladder cancer cells to shear stress comparing morphology to functional performance. T24 cells responded to the shear stress protocol (flow speed of 0.03 ml/min, 3 h) by significantly increasing their surface area. When exposed to deoxynivalenol-3-sulfate (DON-3-Sulf), bladder cells increased this response in a concentration-dependent manner (0.1–1 µM). DON-3-Sulf is a urinary metabolite of a very common food contaminant mycotoxin (deoxynivalenol, DON) and was already described to enhance proliferation of cancer cells. Incubation with DON-3-Sulf also caused the enlargement of the endoplasmic reticulum (ER), decreased the lysosomal movement, and increased the formation of actin stress fibers. Similar remodeling of the endoplasmic reticulum and area spread after shear stress were observed upon incubation with the autophagy activator rapamycin (1–100 nM). Performance of experiments in the presence of chloroquine (chloroquine, 30 μM) further contributed to shed light on the mechanistic link between adaptation to the biomechanical stimulation and ER stress response. At the molecular level, we observed that ER reshaping was linked to actin organization, with the two components mutually regulating each other. Indeed, we identified in the ER stress–cytoskeletal rearrangement an important axis defining the physical/chemical response potential of bladder cells and created a workflow for further investigation of urinary metabolites, food constituents, and contaminants, as well as for pharmacological profiling. Frontiers Media S.A. 2021-05-03 /pmc/articles/PMC8126838/ /pubmed/34012396 http://dx.doi.org/10.3389/fphar.2021.647350 Text en Copyright © 2021 Del Favero, Zeugswetter, Kiss and Marko. 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 Pharmacology
Del Favero, Giorgia
Zeugswetter, Michael
Kiss, Endre
Marko, Doris
Endoplasmic Reticulum Adaptation and Autophagic Competence Shape Response to Fluid Shear Stress in T24 Bladder Cancer Cells
title Endoplasmic Reticulum Adaptation and Autophagic Competence Shape Response to Fluid Shear Stress in T24 Bladder Cancer Cells
title_full Endoplasmic Reticulum Adaptation and Autophagic Competence Shape Response to Fluid Shear Stress in T24 Bladder Cancer Cells
title_fullStr Endoplasmic Reticulum Adaptation and Autophagic Competence Shape Response to Fluid Shear Stress in T24 Bladder Cancer Cells
title_full_unstemmed Endoplasmic Reticulum Adaptation and Autophagic Competence Shape Response to Fluid Shear Stress in T24 Bladder Cancer Cells
title_short Endoplasmic Reticulum Adaptation and Autophagic Competence Shape Response to Fluid Shear Stress in T24 Bladder Cancer Cells
title_sort endoplasmic reticulum adaptation and autophagic competence shape response to fluid shear stress in t24 bladder cancer cells
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8126838/
https://www.ncbi.nlm.nih.gov/pubmed/34012396
http://dx.doi.org/10.3389/fphar.2021.647350
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