Impact of the Nuclear Envelope on Malignant Transformation, Motility, and Survival of Lung Cancer Cells

Abstract Nuclear pore complexes (NPCs) selectively mediate all nucleocytoplasmic transport and engage in fundamental cell‐physiological processes. It is hypothesized that NPCs are critical for malignant transformation and survival of lung cancer cells, and test the hypothesis in lowly and highly met...

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Autores principales:	Sílvio Terra Stefanello, Isabelle Luchtefeld, Ivan Liashkovich, Zoltan Pethö, Ihab Azzam, Etmar Bulk, Gonzalo Rosso, Lilly Döhlinger, Bettina Hesse, Andrea Oeckinghaus, Victor Shahin
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	cancer cellular physiology and biophysics nanomedicine nuclear envelope nuclear pores Science Q
Acceso en línea:	https://doaj.org/article/64ba9750775a4c848ffe9a2230db63df
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spelling	oai:doaj.org-article:64ba9750775a4c848ffe9a2230db63df2021-11-17T08:40:31ZImpact of the Nuclear Envelope on Malignant Transformation, Motility, and Survival of Lung Cancer Cells2198-384410.1002/advs.202102757https://doaj.org/article/64ba9750775a4c848ffe9a2230db63df2021-11-01T00:00:00Zhttps://doi.org/10.1002/advs.202102757https://doaj.org/toc/2198-3844Abstract Nuclear pore complexes (NPCs) selectively mediate all nucleocytoplasmic transport and engage in fundamental cell‐physiological processes. It is hypothesized that NPCs are critical for malignant transformation and survival of lung cancer cells, and test the hypothesis in lowly and highly metastatic non‐small human lung cancer cells (NSCLCs). It is shown that malignant transformation is paralleled by an increased NPCs density, and a balanced pathological weakening of the physiological stringency of the NPC barrier. Pharmacological interference using barrier‐breaking compounds collapses the stringency. Concomitantly, it induces drastic overall structural changes of NSCLCs, terminating their migration. Moreover, the degree of malignancy is found to be paralleled by substantially decreased lamin A/C levels. The latter provides crucial structural and mechanical stability to the nucleus, and interacts with NPCs, cytoskeleton, and nucleoskeleton for cell maintenance, survival, and motility. The recent study reveals the physiological importance of the NPC barrier stringency for mechanical and structural resilience of normal cell nuclei. Hence, reduced lamin A/C levels in conjunction with controlled pathological weakening of the NPC barrier stringency may facilitate deformability of NSCLCs during the metastasis steps. Modulation of the NPC barrier presents a potential strategy for suppressing the malignant phenotype or enhancing the effectiveness of currently existing chemotherapeutics.Sílvio Terra StefanelloIsabelle LuchtefeldIvan LiashkovichZoltan PethöIhab AzzamEtmar BulkGonzalo RossoLilly DöhlingerBettina HesseAndrea OeckinghausVictor ShahinWileyarticlecancercellular physiology and biophysicsnanomedicinenuclear envelopenuclear poresScienceQENAdvanced Science, Vol 8, Iss 22, Pp n/a-n/a (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	cancer cellular physiology and biophysics nanomedicine nuclear envelope nuclear pores Science Q
spellingShingle	cancer cellular physiology and biophysics nanomedicine nuclear envelope nuclear pores Science Q Sílvio Terra Stefanello Isabelle Luchtefeld Ivan Liashkovich Zoltan Pethö Ihab Azzam Etmar Bulk Gonzalo Rosso Lilly Döhlinger Bettina Hesse Andrea Oeckinghaus Victor Shahin Impact of the Nuclear Envelope on Malignant Transformation, Motility, and Survival of Lung Cancer Cells
description	Abstract Nuclear pore complexes (NPCs) selectively mediate all nucleocytoplasmic transport and engage in fundamental cell‐physiological processes. It is hypothesized that NPCs are critical for malignant transformation and survival of lung cancer cells, and test the hypothesis in lowly and highly metastatic non‐small human lung cancer cells (NSCLCs). It is shown that malignant transformation is paralleled by an increased NPCs density, and a balanced pathological weakening of the physiological stringency of the NPC barrier. Pharmacological interference using barrier‐breaking compounds collapses the stringency. Concomitantly, it induces drastic overall structural changes of NSCLCs, terminating their migration. Moreover, the degree of malignancy is found to be paralleled by substantially decreased lamin A/C levels. The latter provides crucial structural and mechanical stability to the nucleus, and interacts with NPCs, cytoskeleton, and nucleoskeleton for cell maintenance, survival, and motility. The recent study reveals the physiological importance of the NPC barrier stringency for mechanical and structural resilience of normal cell nuclei. Hence, reduced lamin A/C levels in conjunction with controlled pathological weakening of the NPC barrier stringency may facilitate deformability of NSCLCs during the metastasis steps. Modulation of the NPC barrier presents a potential strategy for suppressing the malignant phenotype or enhancing the effectiveness of currently existing chemotherapeutics.
format	article
author	Sílvio Terra Stefanello Isabelle Luchtefeld Ivan Liashkovich Zoltan Pethö Ihab Azzam Etmar Bulk Gonzalo Rosso Lilly Döhlinger Bettina Hesse Andrea Oeckinghaus Victor Shahin
author_facet	Sílvio Terra Stefanello Isabelle Luchtefeld Ivan Liashkovich Zoltan Pethö Ihab Azzam Etmar Bulk Gonzalo Rosso Lilly Döhlinger Bettina Hesse Andrea Oeckinghaus Victor Shahin
author_sort	Sílvio Terra Stefanello
title	Impact of the Nuclear Envelope on Malignant Transformation, Motility, and Survival of Lung Cancer Cells
title_short	Impact of the Nuclear Envelope on Malignant Transformation, Motility, and Survival of Lung Cancer Cells
title_full	Impact of the Nuclear Envelope on Malignant Transformation, Motility, and Survival of Lung Cancer Cells
title_fullStr	Impact of the Nuclear Envelope on Malignant Transformation, Motility, and Survival of Lung Cancer Cells
title_full_unstemmed	Impact of the Nuclear Envelope on Malignant Transformation, Motility, and Survival of Lung Cancer Cells
title_sort	impact of the nuclear envelope on malignant transformation, motility, and survival of lung cancer cells
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/64ba9750775a4c848ffe9a2230db63df
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Impact of the Nuclear Envelope on Malignant Transformation, Motility, and Survival of Lung Cancer Cells

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