Stiffening of DU145 prostate cancer cells driven by actin filaments-microtubule crosstalk conferring resistance to microtubule-targeting drugs

Andrzej Kubiak; Matteo Chighizola; Carsten Schulte; Natalia Bryniarska; Julita Wesolowska; Maciej Pudelek; Malgorzata Lasota; Damian Ryszawy; Agnieszka Basta-Kaim; Piotr Laidler; Alessandro Podestà; Malgorzata Lekka

doi:10.1039/d0nr06464e

Stiffening of DU145 prostate cancer cells driven by actin filaments-microtubule crosstalk conferring resistance to microtubule-targeting drugs

Andrzej Kubiak, Matteo Chighizola, Carsten Schulte, Natalia Bryniarska, Julita Wesolowska, Maciej Pudelek, Malgorzata Lasota, Damian Ryszawy, Agnieszka Basta-Kaim, Piotr Laidler, Alessandro Podestà^*, Malgorzata Lekka^*

^*Corresponding author for this work

Biomedical Engineering

Research output: Contribution to journal › Article › peer-review

29 Citations (Scopus)

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Abstract

The crucial role of microtubules in the mitotic-related segregation of chromosomes makes them an excellent target for anticancer microtubule targeting drugs (MTDs) such as vinflunine (VFL), colchicine (COL), and docetaxel (DTX). MTDs affect mitosis by directly perturbing the structural organisation of microtubules. By a direct assessment of the biomechanical properties of prostate cancer DU145 cells exposed to different MTDs using atomic force microscopy, we show that cell stiffening is a response to the application of all the studied MTDs (VFL, COL, DTX). Changes in cellular rigidity are typically attributed to remodelling of the actin filaments in the cytoskeleton. Here, we demonstrate that cell stiffening can be driven by crosstalk between actin filaments and microtubules in MTD-treated cells. Our findings improve the interpretation of biomechanical data obtained for living cells in studies of various physiological and pathological processes.

Original language	English
Pages (from-to)	6212-6226
Number of pages	15
Journal	Nanoscale
Volume	13
Issue number	12
Early online date	26 Feb 2021
DOIs	https://doi.org/10.1039/d0nr06464e
Publication status	Published - 28 Mar 2021

Funding

AK and NB acknowledge the support of InterDokMed project no. POWR.03.02.00-00-I013/16. AP and ML acknowledge the European Union’s support under the Marie Skłodowska-Curie grant agreement No. 812772 (Phys2BioMed). AP and CS acknowledge the European Union’s support under the FET Open grant agreement No. 801126 (EDIT). DR and MP acknowledge the Polish National Science Centre’s support (grant no. UMO-2015/19/D/NZ3/00273). ML and AK are grateful to Mrs Klaudia Suchy for help in cell cultures and to Dr Justyna Bobrowska to record epi-fluorescence images of the cell nucleus.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

stiffening
DU145
prostate cancer cells
actin filaments
cancer cells
microtubule crosstalk
resistance
microtubule-targeting
drugs

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10.1039/d0nr06464e

Kubiak-etal-2021-Stiffening-of-DU145-prostate-cancer-cells-driven-by-actin-filaments-microtubule-crosstalkAccepted author manuscript, 2.3 MBLicence: Strath_1

https://air.unimi.it/handle/2434/907894?mode=complete

Cite this

Kubiak, A., Chighizola, M., Schulte, C., Bryniarska, N., Wesolowska, J., Pudelek, M., Lasota, M., Ryszawy, D., Basta-Kaim, A., Laidler, P., Podestà, A., & Lekka, M. (2021). Stiffening of DU145 prostate cancer cells driven by actin filaments-microtubule crosstalk conferring resistance to microtubule-targeting drugs. Nanoscale, 13(12), 6212-6226. https://doi.org/10.1039/d0nr06464e

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abstract = "The crucial role of microtubules in the mitotic-related segregation of chromosomes makes them an excellent target for anticancer microtubule targeting drugs (MTDs) such as vinflunine (VFL), colchicine (COL), and docetaxel (DTX). MTDs affect mitosis by directly perturbing the structural organisation of microtubules. By a direct assessment of the biomechanical properties of prostate cancer DU145 cells exposed to different MTDs using atomic force microscopy, we show that cell stiffening is a response to the application of all the studied MTDs (VFL, COL, DTX). Changes in cellular rigidity are typically attributed to remodelling of the actin filaments in the cytoskeleton. Here, we demonstrate that cell stiffening can be driven by crosstalk between actin filaments and microtubules in MTD-treated cells. Our findings improve the interpretation of biomechanical data obtained for living cells in studies of various physiological and pathological processes.",

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Kubiak, A, Chighizola, M, Schulte, C, Bryniarska, N, Wesolowska, J, Pudelek, M, Lasota, M, Ryszawy, D, Basta-Kaim, A, Laidler, P, Podestà, A & Lekka, M 2021, 'Stiffening of DU145 prostate cancer cells driven by actin filaments-microtubule crosstalk conferring resistance to microtubule-targeting drugs', Nanoscale, vol. 13, no. 12, pp. 6212-6226. https://doi.org/10.1039/d0nr06464e

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T1 - Stiffening of DU145 prostate cancer cells driven by actin filaments-microtubule crosstalk conferring resistance to microtubule-targeting drugs

AU - Kubiak, Andrzej

AU - Chighizola, Matteo

AU - Schulte, Carsten

AU - Bryniarska, Natalia

AU - Wesolowska, Julita

AU - Pudelek, Maciej

AU - Lasota, Malgorzata

AU - Ryszawy, Damian

AU - Basta-Kaim, Agnieszka

AU - Laidler, Piotr

AU - Podestà, Alessandro

AU - Lekka, Malgorzata

PY - 2021/3/28

Y1 - 2021/3/28

N2 - The crucial role of microtubules in the mitotic-related segregation of chromosomes makes them an excellent target for anticancer microtubule targeting drugs (MTDs) such as vinflunine (VFL), colchicine (COL), and docetaxel (DTX). MTDs affect mitosis by directly perturbing the structural organisation of microtubules. By a direct assessment of the biomechanical properties of prostate cancer DU145 cells exposed to different MTDs using atomic force microscopy, we show that cell stiffening is a response to the application of all the studied MTDs (VFL, COL, DTX). Changes in cellular rigidity are typically attributed to remodelling of the actin filaments in the cytoskeleton. Here, we demonstrate that cell stiffening can be driven by crosstalk between actin filaments and microtubules in MTD-treated cells. Our findings improve the interpretation of biomechanical data obtained for living cells in studies of various physiological and pathological processes.

AB - The crucial role of microtubules in the mitotic-related segregation of chromosomes makes them an excellent target for anticancer microtubule targeting drugs (MTDs) such as vinflunine (VFL), colchicine (COL), and docetaxel (DTX). MTDs affect mitosis by directly perturbing the structural organisation of microtubules. By a direct assessment of the biomechanical properties of prostate cancer DU145 cells exposed to different MTDs using atomic force microscopy, we show that cell stiffening is a response to the application of all the studied MTDs (VFL, COL, DTX). Changes in cellular rigidity are typically attributed to remodelling of the actin filaments in the cytoskeleton. Here, we demonstrate that cell stiffening can be driven by crosstalk between actin filaments and microtubules in MTD-treated cells. Our findings improve the interpretation of biomechanical data obtained for living cells in studies of various physiological and pathological processes.

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KW - resistance

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KW - drugs

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JO - Nanoscale

JF - Nanoscale

IS - 12

ER -

Stiffening of DU145 prostate cancer cells driven by actin filaments-microtubule crosstalk conferring resistance to microtubule-targeting drugs

Abstract

Funding

UN SDGs

Keywords

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