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Upregulation of Thr/Tyr kinase Increases the Cancer Progression by Neurotensin and Dihydropyrimidinase-Like 3 in Lung Cancer

Lung cancer is one of the leading causes of cancer-related death globally, thus elucidation of its molecular pathology is highly highlighted. Aberrant alterations of the spindle assembly checkpoint (SAC) are implicated in the development of cancer due to abnormal cell division. TTK (Thr/Tyr kinase),...

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Autores principales: Tsai, Ying-Ming, Wu, Kuan-Li, Chang, Yung-Yun, Hung, Jen-Yu, Chang, Wei-An, Chang, Chao-Yuan, Jian, Shu-Fang, Tsai, Pei-Hsun, Huang, Yung-Chi, Chong, Inn-Wen, Hsu, Ya-Ling
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7084211/
https://www.ncbi.nlm.nih.gov/pubmed/32121246
http://dx.doi.org/10.3390/ijms21051640
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author Tsai, Ying-Ming
Wu, Kuan-Li
Chang, Yung-Yun
Hung, Jen-Yu
Chang, Wei-An
Chang, Chao-Yuan
Jian, Shu-Fang
Tsai, Pei-Hsun
Huang, Yung-Chi
Chong, Inn-Wen
Hsu, Ya-Ling
author_facet Tsai, Ying-Ming
Wu, Kuan-Li
Chang, Yung-Yun
Hung, Jen-Yu
Chang, Wei-An
Chang, Chao-Yuan
Jian, Shu-Fang
Tsai, Pei-Hsun
Huang, Yung-Chi
Chong, Inn-Wen
Hsu, Ya-Ling
author_sort Tsai, Ying-Ming
collection PubMed
description Lung cancer is one of the leading causes of cancer-related death globally, thus elucidation of its molecular pathology is highly highlighted. Aberrant alterations of the spindle assembly checkpoint (SAC) are implicated in the development of cancer due to abnormal cell division. TTK (Thr/Tyr kinase), a dual serine/threonine kinase, is considered to act as a cancer promoter by controlling SAC. However, the mechanistic details of how TTK-mediated signaling network supports cancer development is still a mystery. Here, we found that TTK was upregulated in the tumor tissue of patients with lung cancer, and enhanced tumor growth and metastasis in vitro and in vivo. Mechanistically, TTK exerted a significant enhancement in cancer growth by neurotensin (NTS) upregulation, and subsequently increased the expression of cyclin A and cdk2, which was resulting in the increase of DNA synthesis. In contrast, TTK increased cell migration and epithelial-to-mesenchymal transition (EMT) by enhancing the expression of dihydropyrimidinase-like 3 (DPYSL3) followed by the increase of snail-regulated EMT, thus reinforce metastatic potential and ultimately tumor metastasis. TTK and DPYSL3 upregulation was positively correlated with a poor clinical outcome in patients with lung cancer. Together, our findings revealed a novel mechanism underlying the oncogenic potential effect of TTK and clarified its downstream factors NTS and DPYSL3 might represent a novel, promising candidate oncogenes with potential therapeutic vulnerabilities in lung cancer.
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spelling pubmed-70842112020-03-24 Upregulation of Thr/Tyr kinase Increases the Cancer Progression by Neurotensin and Dihydropyrimidinase-Like 3 in Lung Cancer Tsai, Ying-Ming Wu, Kuan-Li Chang, Yung-Yun Hung, Jen-Yu Chang, Wei-An Chang, Chao-Yuan Jian, Shu-Fang Tsai, Pei-Hsun Huang, Yung-Chi Chong, Inn-Wen Hsu, Ya-Ling Int J Mol Sci Article Lung cancer is one of the leading causes of cancer-related death globally, thus elucidation of its molecular pathology is highly highlighted. Aberrant alterations of the spindle assembly checkpoint (SAC) are implicated in the development of cancer due to abnormal cell division. TTK (Thr/Tyr kinase), a dual serine/threonine kinase, is considered to act as a cancer promoter by controlling SAC. However, the mechanistic details of how TTK-mediated signaling network supports cancer development is still a mystery. Here, we found that TTK was upregulated in the tumor tissue of patients with lung cancer, and enhanced tumor growth and metastasis in vitro and in vivo. Mechanistically, TTK exerted a significant enhancement in cancer growth by neurotensin (NTS) upregulation, and subsequently increased the expression of cyclin A and cdk2, which was resulting in the increase of DNA synthesis. In contrast, TTK increased cell migration and epithelial-to-mesenchymal transition (EMT) by enhancing the expression of dihydropyrimidinase-like 3 (DPYSL3) followed by the increase of snail-regulated EMT, thus reinforce metastatic potential and ultimately tumor metastasis. TTK and DPYSL3 upregulation was positively correlated with a poor clinical outcome in patients with lung cancer. Together, our findings revealed a novel mechanism underlying the oncogenic potential effect of TTK and clarified its downstream factors NTS and DPYSL3 might represent a novel, promising candidate oncogenes with potential therapeutic vulnerabilities in lung cancer. MDPI 2020-02-28 /pmc/articles/PMC7084211/ /pubmed/32121246 http://dx.doi.org/10.3390/ijms21051640 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Tsai, Ying-Ming
Wu, Kuan-Li
Chang, Yung-Yun
Hung, Jen-Yu
Chang, Wei-An
Chang, Chao-Yuan
Jian, Shu-Fang
Tsai, Pei-Hsun
Huang, Yung-Chi
Chong, Inn-Wen
Hsu, Ya-Ling
Upregulation of Thr/Tyr kinase Increases the Cancer Progression by Neurotensin and Dihydropyrimidinase-Like 3 in Lung Cancer
title Upregulation of Thr/Tyr kinase Increases the Cancer Progression by Neurotensin and Dihydropyrimidinase-Like 3 in Lung Cancer
title_full Upregulation of Thr/Tyr kinase Increases the Cancer Progression by Neurotensin and Dihydropyrimidinase-Like 3 in Lung Cancer
title_fullStr Upregulation of Thr/Tyr kinase Increases the Cancer Progression by Neurotensin and Dihydropyrimidinase-Like 3 in Lung Cancer
title_full_unstemmed Upregulation of Thr/Tyr kinase Increases the Cancer Progression by Neurotensin and Dihydropyrimidinase-Like 3 in Lung Cancer
title_short Upregulation of Thr/Tyr kinase Increases the Cancer Progression by Neurotensin and Dihydropyrimidinase-Like 3 in Lung Cancer
title_sort upregulation of thr/tyr kinase increases the cancer progression by neurotensin and dihydropyrimidinase-like 3 in lung cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7084211/
https://www.ncbi.nlm.nih.gov/pubmed/32121246
http://dx.doi.org/10.3390/ijms21051640
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