Loss of DSTYK activates Wnt/β-catenin signaling and glycolysis in lung adenocarcinoma

Abstract Aberrant activation of Wnt/β-catenin signaling and dysregulation of metabolism have been frequently observed in lung cancer. However, the molecular mechanism by which Wnt/β-catenin signaling is regulated and the link between Wnt/β-catenin signaling and cancer metabolism are not fully unders...

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Autores principales:	Chenxi Zhong, Ming Chen, Yu Chen, Feng Yao, Wentao Fang
Formato:	article
Lenguaje:	EN
Publicado:	Nature Publishing Group 2021
Materias:	Cytology QH573-671
Acceso en línea:	https://doaj.org/article/3fc6feca7773460b921414082930e6c8
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spelling	oai:doaj.org-article:3fc6feca7773460b921414082930e6c82021-12-05T12:04:22ZLoss of DSTYK activates Wnt/β-catenin signaling and glycolysis in lung adenocarcinoma10.1038/s41419-021-04385-12041-4889https://doaj.org/article/3fc6feca7773460b921414082930e6c82021-12-01T00:00:00Zhttps://doi.org/10.1038/s41419-021-04385-1https://doaj.org/toc/2041-4889Abstract Aberrant activation of Wnt/β-catenin signaling and dysregulation of metabolism have been frequently observed in lung cancer. However, the molecular mechanism by which Wnt/β-catenin signaling is regulated and the link between Wnt/β-catenin signaling and cancer metabolism are not fully understood. In this study, we showed that the loss of dual serine/threonine tyrosine protein kinase (DSTYK) led to the activation of Wnt/β-catenin signaling and upregulation of its target gene, lactate dehydrogenase (LDHA), and thus the elevation of lactate. DSTYK phosphorylated the N-terminal domain of β-catenin and inhibited Wnt/β-catenin signaling, which led to the inhibition of cell growth, colony formation and tumorigenesis in a lung adenocarcinoma mouse model. DSTYK was downregulated in lung cancer tissues, and its expression was positively correlated with the survival of patients with lung adenocarcinoma. Taken together, these results demonstrate that the loss of DSTYK activates Wnt/β-catenin/LDHA signaling to promote the tumorigenesis of lung cancer and that DSTYK may be a therapeutic target.Chenxi ZhongMing ChenYu ChenFeng YaoWentao FangNature Publishing GrouparticleCytologyQH573-671ENCell Death and Disease, Vol 12, Iss 12, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Cytology QH573-671
spellingShingle	Cytology QH573-671 Chenxi Zhong Ming Chen Yu Chen Feng Yao Wentao Fang Loss of DSTYK activates Wnt/β-catenin signaling and glycolysis in lung adenocarcinoma
description	Abstract Aberrant activation of Wnt/β-catenin signaling and dysregulation of metabolism have been frequently observed in lung cancer. However, the molecular mechanism by which Wnt/β-catenin signaling is regulated and the link between Wnt/β-catenin signaling and cancer metabolism are not fully understood. In this study, we showed that the loss of dual serine/threonine tyrosine protein kinase (DSTYK) led to the activation of Wnt/β-catenin signaling and upregulation of its target gene, lactate dehydrogenase (LDHA), and thus the elevation of lactate. DSTYK phosphorylated the N-terminal domain of β-catenin and inhibited Wnt/β-catenin signaling, which led to the inhibition of cell growth, colony formation and tumorigenesis in a lung adenocarcinoma mouse model. DSTYK was downregulated in lung cancer tissues, and its expression was positively correlated with the survival of patients with lung adenocarcinoma. Taken together, these results demonstrate that the loss of DSTYK activates Wnt/β-catenin/LDHA signaling to promote the tumorigenesis of lung cancer and that DSTYK may be a therapeutic target.
format	article
author	Chenxi Zhong Ming Chen Yu Chen Feng Yao Wentao Fang
author_facet	Chenxi Zhong Ming Chen Yu Chen Feng Yao Wentao Fang
author_sort	Chenxi Zhong
title	Loss of DSTYK activates Wnt/β-catenin signaling and glycolysis in lung adenocarcinoma
title_short	Loss of DSTYK activates Wnt/β-catenin signaling and glycolysis in lung adenocarcinoma
title_full	Loss of DSTYK activates Wnt/β-catenin signaling and glycolysis in lung adenocarcinoma
title_fullStr	Loss of DSTYK activates Wnt/β-catenin signaling and glycolysis in lung adenocarcinoma
title_full_unstemmed	Loss of DSTYK activates Wnt/β-catenin signaling and glycolysis in lung adenocarcinoma
title_sort	loss of dstyk activates wnt/β-catenin signaling and glycolysis in lung adenocarcinoma
publisher	Nature Publishing Group
publishDate	2021
url	https://doaj.org/article/3fc6feca7773460b921414082930e6c8
work_keys_str_mv	AT chenxizhong lossofdstykactivateswntbcateninsignalingandglycolysisinlungadenocarcinoma AT mingchen lossofdstykactivateswntbcateninsignalingandglycolysisinlungadenocarcinoma AT yuchen lossofdstykactivateswntbcateninsignalingandglycolysisinlungadenocarcinoma AT fengyao lossofdstykactivateswntbcateninsignalingandglycolysisinlungadenocarcinoma AT wentaofang lossofdstykactivateswntbcateninsignalingandglycolysisinlungadenocarcinoma
_version_	1718372248505548800

Loss of DSTYK activates Wnt/β-catenin signaling and glycolysis in lung adenocarcinoma

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