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Phosphorylation of LZTS2 by PLK1 activates the Wnt pathway.
- Source :
-
Cellular signalling [Cell Signal] 2024 Aug; Vol. 120, pp. 111226. Date of Electronic Publication: 2024 May 11. - Publication Year :
- 2024
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Abstract
- Lung adenocarcinoma (LUAD), responsible for nearly half of lung cancer cases, is one of the most prevalent and lethal malignant tumors globally. There is increasing evidence suggesting that the oncoprotein PLK1 plays a role in the onset and advancement of different types of cancer, including LUAD. Nonetheless, the precise mechanism by which PLK1 promotes tumorigenesis remains unclear. In this study, we demonstrate the upregulation of PLK1 in LUAD samples, which leads to a poor prognosis for LUAD patients. Intriguingly, PLK1 enables to bind to LZTS2 and promote its phosphorylation without affecting LZTS2 degradation. Furthermore, we identify that Ser451 is a key phosphorylation site in LZTS2 protein. LZTS2 exerts an anti-tumor effect by restricting the translocation of the transcription factor β-Catenin into the nucleus, thereby suppressing the Wnt pathway. PLK1 disrupts the interaction between LZTS2 and β-Catenin, resulting in the nuclear accumulation of β-Catenin and the activation of the Wnt pathway. Additionally, we reveal that LZTS2 inhibits the proliferation and migration of LUAD cells, which is rescued by PLK1. Finally, PLK1 inhibitors exhibit a dose-dependent suppression of LUAD cell proliferation and migration. Collectively, this study uncovers the pro-tumorigenic mechanism of PLK1, positioning it as a promising therapeutic target for Wnt-related LUAD.<br />Competing Interests: Declaration of competing interest The authors declare no potential conflicts of interest with respect to the research, authorship and publication of this article.<br /> (Copyright © 2024. Published by Elsevier Inc.)
- Subjects :
- Animals
Humans
Adenocarcinoma of Lung metabolism
Adenocarcinoma of Lung pathology
Adenocarcinoma of Lung genetics
Cell Line, Tumor
Cell Movement
Phosphorylation
beta Catenin metabolism
Cell Cycle Proteins metabolism
Cell Proliferation
Lung Neoplasms metabolism
Lung Neoplasms pathology
Polo-Like Kinase 1
Protein Serine-Threonine Kinases metabolism
Proto-Oncogene Proteins metabolism
Wnt Signaling Pathway
Subjects
Details
- Language :
- English
- ISSN :
- 1873-3913
- Volume :
- 120
- Database :
- MEDLINE
- Journal :
- Cellular signalling
- Publication Type :
- Academic Journal
- Accession number :
- 38740232
- Full Text :
- https://doi.org/10.1016/j.cellsig.2024.111226