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Shwachman-Bodian-Diamond syndrome protein desensitizes breast cancer cells to apoptosis in stiff matrices by repressing the caspase 8-mediated pathway

Certain cancer types, including breast cancer, are accompanied with stiffening of the surrounding extracellular matrix (ECM). Previous studies suggest that this stiffened matrix influences cancer cell progression, such as proliferation and invasion, both biochemically and mechanically. However, the...

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Autores principales: Lee, Jieun, Ko, Panseon, You, Eunae, Jeong, Jangho, Keum, Seula, Kim, Jaegu, Rahman, Mizanur, Lee, Dong Ho, Rhee, Sangmyung
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6913620/
https://www.ncbi.nlm.nih.gov/pubmed/31853379
http://dx.doi.org/10.1080/19768354.2019.1666030
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author Lee, Jieun
Ko, Panseon
You, Eunae
Jeong, Jangho
Keum, Seula
Kim, Jaegu
Rahman, Mizanur
Lee, Dong Ho
Rhee, Sangmyung
author_facet Lee, Jieun
Ko, Panseon
You, Eunae
Jeong, Jangho
Keum, Seula
Kim, Jaegu
Rahman, Mizanur
Lee, Dong Ho
Rhee, Sangmyung
author_sort Lee, Jieun
collection PubMed
description Certain cancer types, including breast cancer, are accompanied with stiffening of the surrounding extracellular matrix (ECM). Previous studies suggest that this stiffened matrix influences cancer cell progression, such as proliferation and invasion, both biochemically and mechanically. However, the contribution of ECM stiffness to cellular response to diverse stresses, which most cancer cells are exposed to, has not been elucidated. In this study, we demonstrate that expression of the Shwachman-Bodian-Diamond syndrome protein (SDBS) in a stiff matrix protects cells from apoptosis induced by environmental stress, including anticancer drugs. Cells cultured on stiff matrices were less apoptotic process induced by serum depletion than those cultured on the soft matrix. Interestingly, knockdown (KD) of SDBS among the apoptosis-related genes significantly increased apoptosis induced by serum depletion in cells cultured in a stiff matrix. Apoptosis of SDBS KD cells in a stiff matrix was significantly inhibited by the caspase 8 inhibitor, indicating that activation of the caspase 8 pathway by SDBS KD is critical for cancer cell apoptosis in stiff matrices. Additionally, we also found that downregulation of SDBS also effectively increased cell death induced by anticancer drugs, including paclitaxel, cisplatin, and eribulin. Taken together, our findings suggest that inhibition of SDBS enhances effective chemotherapy of malignant breast cancer cells in stiff ECM environments.
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spelling pubmed-69136202019-12-18 Shwachman-Bodian-Diamond syndrome protein desensitizes breast cancer cells to apoptosis in stiff matrices by repressing the caspase 8-mediated pathway Lee, Jieun Ko, Panseon You, Eunae Jeong, Jangho Keum, Seula Kim, Jaegu Rahman, Mizanur Lee, Dong Ho Rhee, Sangmyung Anim Cells Syst (Seoul) Molecular & Cellular Biology Certain cancer types, including breast cancer, are accompanied with stiffening of the surrounding extracellular matrix (ECM). Previous studies suggest that this stiffened matrix influences cancer cell progression, such as proliferation and invasion, both biochemically and mechanically. However, the contribution of ECM stiffness to cellular response to diverse stresses, which most cancer cells are exposed to, has not been elucidated. In this study, we demonstrate that expression of the Shwachman-Bodian-Diamond syndrome protein (SDBS) in a stiff matrix protects cells from apoptosis induced by environmental stress, including anticancer drugs. Cells cultured on stiff matrices were less apoptotic process induced by serum depletion than those cultured on the soft matrix. Interestingly, knockdown (KD) of SDBS among the apoptosis-related genes significantly increased apoptosis induced by serum depletion in cells cultured in a stiff matrix. Apoptosis of SDBS KD cells in a stiff matrix was significantly inhibited by the caspase 8 inhibitor, indicating that activation of the caspase 8 pathway by SDBS KD is critical for cancer cell apoptosis in stiff matrices. Additionally, we also found that downregulation of SDBS also effectively increased cell death induced by anticancer drugs, including paclitaxel, cisplatin, and eribulin. Taken together, our findings suggest that inhibition of SDBS enhances effective chemotherapy of malignant breast cancer cells in stiff ECM environments. Taylor & Francis 2019-09-20 /pmc/articles/PMC6913620/ /pubmed/31853379 http://dx.doi.org/10.1080/19768354.2019.1666030 Text en © 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Molecular & Cellular Biology
Lee, Jieun
Ko, Panseon
You, Eunae
Jeong, Jangho
Keum, Seula
Kim, Jaegu
Rahman, Mizanur
Lee, Dong Ho
Rhee, Sangmyung
Shwachman-Bodian-Diamond syndrome protein desensitizes breast cancer cells to apoptosis in stiff matrices by repressing the caspase 8-mediated pathway
title Shwachman-Bodian-Diamond syndrome protein desensitizes breast cancer cells to apoptosis in stiff matrices by repressing the caspase 8-mediated pathway
title_full Shwachman-Bodian-Diamond syndrome protein desensitizes breast cancer cells to apoptosis in stiff matrices by repressing the caspase 8-mediated pathway
title_fullStr Shwachman-Bodian-Diamond syndrome protein desensitizes breast cancer cells to apoptosis in stiff matrices by repressing the caspase 8-mediated pathway
title_full_unstemmed Shwachman-Bodian-Diamond syndrome protein desensitizes breast cancer cells to apoptosis in stiff matrices by repressing the caspase 8-mediated pathway
title_short Shwachman-Bodian-Diamond syndrome protein desensitizes breast cancer cells to apoptosis in stiff matrices by repressing the caspase 8-mediated pathway
title_sort shwachman-bodian-diamond syndrome protein desensitizes breast cancer cells to apoptosis in stiff matrices by repressing the caspase 8-mediated pathway
topic Molecular & Cellular Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6913620/
https://www.ncbi.nlm.nih.gov/pubmed/31853379
http://dx.doi.org/10.1080/19768354.2019.1666030
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