An TRIM59-CDK6 axis regulates growth and metastasis of lung cancer
| Autor: | Lijing wang, Biao Geng, Hanli wang, Xianhui pan, Lilong qin, Manman Liang, Wenying Zhao, Xingwu Chen |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
MAPK/ERK pathway Epithelial-Mesenchymal Transition Lung Neoplasms CDK6 MAP Kinase Signaling System Metastasis Tripartite Motif Proteins 03 medical and health sciences 0302 clinical medicine Cell Movement Cell Line Tumor Nitriles Biomarkers Tumor Butadienes medicine Carcinoma Humans TRIM59 Neoplasm Metastasis Protein kinase A Lung cancer Cell Proliferation biology EMT Intracellular Signaling Peptides and Proteins Original Articles Cyclin-Dependent Kinase 6 Cell Biology medicine.disease Hedgehog signaling pathway Gene Expression Regulation Neoplastic lung cancer 030104 developmental biology 030220 oncology & carcinogenesis biology.protein Cancer research Molecular Medicine Immunohistochemistry Original Article ERK pathway Cyclin-dependent kinase 6 Signal Transduction |
| Zdroj: | Journal of Cellular and Molecular Medicine |
| ISSN: | 1582-1838 |
| Popis: | Lung cancer (LC) is a devastating malignancy with no effective treatments, due to its complex genomic profile. Using bioinformatics analysis and immunohistochemical of lung carcinoma tissues, we show that TRIM59 as a critical oncoprotein relating to LC proliferation and metastasis. In this study, high TRIM59 expression was significantly correlated with lymph node metastasis, distant metastasis, and tumour stage. Furthermore, up‐regulation of TRIM59 expression correlated with poorer outcomes in LC patients. Mechanistically, TRIM59 play a key role in promoting LC growth and metastasis through regulation of extracellular‐signal regulated protein kinase (ERK) signalling pathway and epithelial‐to‐mesenchymal transition (EMT)‐markers, as validated by loss‐of‐function studies. In‐depth bioinformatics analysis showed that there is preliminary evidence of co‐expression of TRIM59 and cyclin dependent kinase 6 (CDK6) in LC. Notably, CDK6 expression significantly decreased when TRIM59 was knocked down in the LC cells. In contrast, exogenous up‐regulation of TRIM59 expression also induced significant increases in the expression of CDK6. Moreover, the expression of CDK6 was also inhibited by the ERK signalling inhibitor, U0126. The results of both loss‐ and gain‐of‐function studies showed that TRIM59 could regulate the expression of CDK6. Collectively, these data provide evidence that TRIM59 is involved in lung carcinoma growth and progression possibly through the induction of CDK6 expression and EMT process by activation of ERK pathway. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text