A novel aminothiazole KY-05009 with potential to inhibit Traf2- and Nck-interacting kinase (TNIK) attenuates TGF-β1-mediated epithelial-to-mesenchymal transition in human lung adenocarcinoma A549 cells.

Transforming growth factor (TGF)-β triggers the epithelial-to-mesenchymal transition (EMT) of cancer cells via well-orchestrated crosstalk between Smad and non-Smad signaling pathways, including Wnt/β-catenin. Since EMT-induced motility and invasion play a critical role in cancer metastasis, EMT-rel...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Jiyeon Kim, Seong-Hee Moon, Bum Tae Kim, Chong Hak Chae, Joo Yun Lee, Seong Hwan Kim
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/12a7dc3576f440df86eb6609771912f1
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:12a7dc3576f440df86eb6609771912f1
record_format	dspace
spelling	oai:doaj.org-article:12a7dc3576f440df86eb6609771912f12021-11-25T05:55:38ZA novel aminothiazole KY-05009 with potential to inhibit Traf2- and Nck-interacting kinase (TNIK) attenuates TGF-β1-mediated epithelial-to-mesenchymal transition in human lung adenocarcinoma A549 cells.1932-620310.1371/journal.pone.0110180https://doaj.org/article/12a7dc3576f440df86eb6609771912f12014-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0110180https://doaj.org/toc/1932-6203Transforming growth factor (TGF)-β triggers the epithelial-to-mesenchymal transition (EMT) of cancer cells via well-orchestrated crosstalk between Smad and non-Smad signaling pathways, including Wnt/β-catenin. Since EMT-induced motility and invasion play a critical role in cancer metastasis, EMT-related molecules are emerging as novel targets of anti-cancer therapies. Traf2- and Nck-interacting kinase (TNIK) has recently been considered as a first-in-class anti-cancer target molecule to regulate Wnt signaling pathway, but pharmacologic inhibition of its EMT activity has not yet been studied. Here, using 5-(4-methylbenzamido)-2-(phenylamino)thiazole-4-carboxamide (KY-05009) with TNIK-inhibitory activity, its efficacy to inhibit EMT in cancer cells was validated. The molecular docking/binding study revealed the binding of KY-05009 in the hinge region of TNIK, and the inhibitory activity of KY-05009 against TNIK was confirmed by an ATP competition assay (Ki, 100 nM). In A549 cells, KY-05009 significantly and strongly inhibited the TGF-β-activated EMT through the attenuation of Smad and non-Smad signaling pathways, including the Wnt, NF-κB, FAK-Src-paxillin-related focal adhesion, and MAP kinases (ERK and JNK) signaling pathways. Continuing efforts to identify and validate potential therapeutic targets associated with EMT, such as TNIK, provide new and improved therapies for treating and/or preventing EMT-based disorders, such as cancer metastasis and fibrosis.Jiyeon KimSeong-Hee MoonBum Tae KimChong Hak ChaeJoo Yun LeeSeong Hwan KimPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 10, p e110180 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jiyeon Kim Seong-Hee Moon Bum Tae Kim Chong Hak Chae Joo Yun Lee Seong Hwan Kim A novel aminothiazole KY-05009 with potential to inhibit Traf2- and Nck-interacting kinase (TNIK) attenuates TGF-β1-mediated epithelial-to-mesenchymal transition in human lung adenocarcinoma A549 cells.
description	Transforming growth factor (TGF)-β triggers the epithelial-to-mesenchymal transition (EMT) of cancer cells via well-orchestrated crosstalk between Smad and non-Smad signaling pathways, including Wnt/β-catenin. Since EMT-induced motility and invasion play a critical role in cancer metastasis, EMT-related molecules are emerging as novel targets of anti-cancer therapies. Traf2- and Nck-interacting kinase (TNIK) has recently been considered as a first-in-class anti-cancer target molecule to regulate Wnt signaling pathway, but pharmacologic inhibition of its EMT activity has not yet been studied. Here, using 5-(4-methylbenzamido)-2-(phenylamino)thiazole-4-carboxamide (KY-05009) with TNIK-inhibitory activity, its efficacy to inhibit EMT in cancer cells was validated. The molecular docking/binding study revealed the binding of KY-05009 in the hinge region of TNIK, and the inhibitory activity of KY-05009 against TNIK was confirmed by an ATP competition assay (Ki, 100 nM). In A549 cells, KY-05009 significantly and strongly inhibited the TGF-β-activated EMT through the attenuation of Smad and non-Smad signaling pathways, including the Wnt, NF-κB, FAK-Src-paxillin-related focal adhesion, and MAP kinases (ERK and JNK) signaling pathways. Continuing efforts to identify and validate potential therapeutic targets associated with EMT, such as TNIK, provide new and improved therapies for treating and/or preventing EMT-based disorders, such as cancer metastasis and fibrosis.
format	article
author	Jiyeon Kim Seong-Hee Moon Bum Tae Kim Chong Hak Chae Joo Yun Lee Seong Hwan Kim
author_facet	Jiyeon Kim Seong-Hee Moon Bum Tae Kim Chong Hak Chae Joo Yun Lee Seong Hwan Kim
author_sort	Jiyeon Kim
title	A novel aminothiazole KY-05009 with potential to inhibit Traf2- and Nck-interacting kinase (TNIK) attenuates TGF-β1-mediated epithelial-to-mesenchymal transition in human lung adenocarcinoma A549 cells.
title_short	A novel aminothiazole KY-05009 with potential to inhibit Traf2- and Nck-interacting kinase (TNIK) attenuates TGF-β1-mediated epithelial-to-mesenchymal transition in human lung adenocarcinoma A549 cells.
title_full	A novel aminothiazole KY-05009 with potential to inhibit Traf2- and Nck-interacting kinase (TNIK) attenuates TGF-β1-mediated epithelial-to-mesenchymal transition in human lung adenocarcinoma A549 cells.
title_fullStr	A novel aminothiazole KY-05009 with potential to inhibit Traf2- and Nck-interacting kinase (TNIK) attenuates TGF-β1-mediated epithelial-to-mesenchymal transition in human lung adenocarcinoma A549 cells.
title_full_unstemmed	A novel aminothiazole KY-05009 with potential to inhibit Traf2- and Nck-interacting kinase (TNIK) attenuates TGF-β1-mediated epithelial-to-mesenchymal transition in human lung adenocarcinoma A549 cells.
title_sort	novel aminothiazole ky-05009 with potential to inhibit traf2- and nck-interacting kinase (tnik) attenuates tgf-β1-mediated epithelial-to-mesenchymal transition in human lung adenocarcinoma a549 cells.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/12a7dc3576f440df86eb6609771912f1
work_keys_str_mv	AT jiyeonkim anovelaminothiazoleky05009withpotentialtoinhibittraf2andnckinteractingkinasetnikattenuatestgfb1mediatedepithelialtomesenchymaltransitioninhumanlungadenocarcinomaa549cells AT seongheemoon anovelaminothiazoleky05009withpotentialtoinhibittraf2andnckinteractingkinasetnikattenuatestgfb1mediatedepithelialtomesenchymaltransitioninhumanlungadenocarcinomaa549cells AT bumtaekim anovelaminothiazoleky05009withpotentialtoinhibittraf2andnckinteractingkinasetnikattenuatestgfb1mediatedepithelialtomesenchymaltransitioninhumanlungadenocarcinomaa549cells AT chonghakchae anovelaminothiazoleky05009withpotentialtoinhibittraf2andnckinteractingkinasetnikattenuatestgfb1mediatedepithelialtomesenchymaltransitioninhumanlungadenocarcinomaa549cells AT jooyunlee anovelaminothiazoleky05009withpotentialtoinhibittraf2andnckinteractingkinasetnikattenuatestgfb1mediatedepithelialtomesenchymaltransitioninhumanlungadenocarcinomaa549cells AT seonghwankim anovelaminothiazoleky05009withpotentialtoinhibittraf2andnckinteractingkinasetnikattenuatestgfb1mediatedepithelialtomesenchymaltransitioninhumanlungadenocarcinomaa549cells AT jiyeonkim novelaminothiazoleky05009withpotentialtoinhibittraf2andnckinteractingkinasetnikattenuatestgfb1mediatedepithelialtomesenchymaltransitioninhumanlungadenocarcinomaa549cells AT seongheemoon novelaminothiazoleky05009withpotentialtoinhibittraf2andnckinteractingkinasetnikattenuatestgfb1mediatedepithelialtomesenchymaltransitioninhumanlungadenocarcinomaa549cells AT bumtaekim novelaminothiazoleky05009withpotentialtoinhibittraf2andnckinteractingkinasetnikattenuatestgfb1mediatedepithelialtomesenchymaltransitioninhumanlungadenocarcinomaa549cells AT chonghakchae novelaminothiazoleky05009withpotentialtoinhibittraf2andnckinteractingkinasetnikattenuatestgfb1mediatedepithelialtomesenchymaltransitioninhumanlungadenocarcinomaa549cells AT jooyunlee novelaminothiazoleky05009withpotentialtoinhibittraf2andnckinteractingkinasetnikattenuatestgfb1mediatedepithelialtomesenchymaltransitioninhumanlungadenocarcinomaa549cells AT seonghwankim novelaminothiazoleky05009withpotentialtoinhibittraf2andnckinteractingkinasetnikattenuatestgfb1mediatedepithelialtomesenchymaltransitioninhumanlungadenocarcinomaa549cells
_version_	1718414324405370880

A novel aminothiazole KY-05009 with potential to inhibit Traf2- and Nck-interacting kinase (TNIK) attenuates TGF-β1-mediated epithelial-to-mesenchymal transition in human lung adenocarcinoma A549 cells.

Ejemplares similares