Cell softening in malignant progression of human lung cancer cells by activation of receptor tyrosine kinase AXL

Abstract To study the role of cell softening in malignant progression, Transwell assay and atomic force microscope were used to classify six human non-small cell lung cancer cell lines into two groups: a high motility-low stiffness (HMLS) group and a low motility-high stiffness (LMHS) group. We foun...

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Autores principales:	Keisuke Iida, Ryo Sakai, Shota Yokoyama, Naritaka Kobayashi, Shodai Togo, Hiroshi Y. Yoshikawa, Anchalee Rawangkan, Kozue Namiki, Masami Suganuma
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a557dc64c7504b61bb974bc013633a1e
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spelling	oai:doaj.org-article:a557dc64c7504b61bb974bc013633a1e2021-12-02T15:05:40ZCell softening in malignant progression of human lung cancer cells by activation of receptor tyrosine kinase AXL10.1038/s41598-017-18120-42045-2322https://doaj.org/article/a557dc64c7504b61bb974bc013633a1e2017-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-18120-4https://doaj.org/toc/2045-2322Abstract To study the role of cell softening in malignant progression, Transwell assay and atomic force microscope were used to classify six human non-small cell lung cancer cell lines into two groups: a high motility-low stiffness (HMLS) group and a low motility-high stiffness (LMHS) group. We found a significant role of activity of the AXL receptor tyrosine kinase, which belongs to the TAM (Tyro3, AXL, Mer) family, in the stimulation of motility and cell softening. HMLS cells expressed higher AXL levels than LMHS cells and contained phosphorylated AXL. H1703 LMHS cells transfected with exogenous AXL exhibited increased motility and decreased stiffness, with low levels of actin stress fibre formation. Conversely, the AXL-specific inhibitor R428 and AXL-targeting siRNA reduced motility and increased stiffness in H1299 HMLS cells. Knockdown of AXL stimulated actin stress fibre formation, which inhibited tumour formation in a mouse xenograft model. The Ras/Rac inhibitor SCH 51344, which blocks disruption of actin stress fibres, exerted similar effects to AXL inactivation. We therefore propose that the Ras/Rac pathway operates downstream of AXL. Thus, AXL activation-induced cell softening promotes malignant progression in non-small cell lung cancer and represents a key biophysical property of cancer cells.Keisuke IidaRyo SakaiShota YokoyamaNaritaka KobayashiShodai TogoHiroshi Y. YoshikawaAnchalee RawangkanKozue NamikiMasami SuganumaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Keisuke Iida Ryo Sakai Shota Yokoyama Naritaka Kobayashi Shodai Togo Hiroshi Y. Yoshikawa Anchalee Rawangkan Kozue Namiki Masami Suganuma Cell softening in malignant progression of human lung cancer cells by activation of receptor tyrosine kinase AXL
description	Abstract To study the role of cell softening in malignant progression, Transwell assay and atomic force microscope were used to classify six human non-small cell lung cancer cell lines into two groups: a high motility-low stiffness (HMLS) group and a low motility-high stiffness (LMHS) group. We found a significant role of activity of the AXL receptor tyrosine kinase, which belongs to the TAM (Tyro3, AXL, Mer) family, in the stimulation of motility and cell softening. HMLS cells expressed higher AXL levels than LMHS cells and contained phosphorylated AXL. H1703 LMHS cells transfected with exogenous AXL exhibited increased motility and decreased stiffness, with low levels of actin stress fibre formation. Conversely, the AXL-specific inhibitor R428 and AXL-targeting siRNA reduced motility and increased stiffness in H1299 HMLS cells. Knockdown of AXL stimulated actin stress fibre formation, which inhibited tumour formation in a mouse xenograft model. The Ras/Rac inhibitor SCH 51344, which blocks disruption of actin stress fibres, exerted similar effects to AXL inactivation. We therefore propose that the Ras/Rac pathway operates downstream of AXL. Thus, AXL activation-induced cell softening promotes malignant progression in non-small cell lung cancer and represents a key biophysical property of cancer cells.
format	article
author	Keisuke Iida Ryo Sakai Shota Yokoyama Naritaka Kobayashi Shodai Togo Hiroshi Y. Yoshikawa Anchalee Rawangkan Kozue Namiki Masami Suganuma
author_facet	Keisuke Iida Ryo Sakai Shota Yokoyama Naritaka Kobayashi Shodai Togo Hiroshi Y. Yoshikawa Anchalee Rawangkan Kozue Namiki Masami Suganuma
author_sort	Keisuke Iida
title	Cell softening in malignant progression of human lung cancer cells by activation of receptor tyrosine kinase AXL
title_short	Cell softening in malignant progression of human lung cancer cells by activation of receptor tyrosine kinase AXL
title_full	Cell softening in malignant progression of human lung cancer cells by activation of receptor tyrosine kinase AXL
title_fullStr	Cell softening in malignant progression of human lung cancer cells by activation of receptor tyrosine kinase AXL
title_full_unstemmed	Cell softening in malignant progression of human lung cancer cells by activation of receptor tyrosine kinase AXL
title_sort	cell softening in malignant progression of human lung cancer cells by activation of receptor tyrosine kinase axl
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/a557dc64c7504b61bb974bc013633a1e
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_version_	1718388785561993216

Cell softening in malignant progression of human lung cancer cells by activation of receptor tyrosine kinase AXL

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