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1.
Cell Signal ; 120: 111226, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38740232

RESUMEN

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 ß-Catenin into the nucleus, thereby suppressing the Wnt pathway. PLK1 disrupts the interaction between LZTS2 and ß-Catenin, resulting in the nuclear accumulation of ß-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.


Asunto(s)
Proteínas de Ciclo Celular , Proliferación Celular , Neoplasias Pulmonares , Quinasa Tipo Polo 1 , Proteínas Serina-Treonina Quinasas , Proteínas Proto-Oncogénicas , Vía de Señalización Wnt , beta Catenina , Animales , Humanos , Adenocarcinoma del Pulmón/metabolismo , Adenocarcinoma del Pulmón/patología , Adenocarcinoma del Pulmón/genética , beta Catenina/metabolismo , Proteínas de Ciclo Celular/metabolismo , Línea Celular Tumoral , Movimiento Celular , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Fosforilación , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Proto-Oncogénicas/metabolismo
2.
Front Bioeng Biotechnol ; 9: 671879, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34055763

RESUMEN

Compared with endophytes, metabolites from endophytes (MEs) have great potential in agriculture. However, a technique for industrializing the production of MEs is still scarce. Moreover, the establishment of effective methods for evaluating the quality of MEs is hampered by the fact that some compounds with beneficial effects on crops have not been clearly identified. Herein, a system was established for the production, quality control and application of MEs by using the extract from Paecilomyces variotii SJ1 (ZNC). First, the extraction conditions of ZNC were optimized through response surface methodology, after which each batch (500 L) met the consumption requirements of crops in 7,467 hectares. Then, chromatographic fingerprinting and enzyme-linked immunosorbent assay were applied to evaluate the similarity and specificity of unknown effective components in ZNC, ensuring a similarity of more than 90% and a quantitative accuracy of greater than 99.9% for the products from different batches. Finally, the bioactivity of industrially produced ZNC was evaluated in the field, and it significantly increased the potato yields by 4.4-10.8%. Overall, we have established a practical technical system for the large-scale application of ZNC in agriculture.

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