Angiomotin decreases lung cancer progression by sequestering oncogenic YAP/TAZ and decreasing Cyr61 expression
| Autor: | Ming Shyan Huang, Shah-Hwa Chou, Po-Lin Kuo, Hsu Yl, Ming-Ju Tsai, Ya-Wen Ho, Chiang Sy, Yi-Shiuan Lin, Cheng-Ying Wu, Jen-Yu Hung |
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| Rok vydání: | 2014 |
| Předmět: |
Cancer Research
Lung Neoplasms Down-Regulation Mice Nude Adenocarcinoma of Lung Cell Cycle Proteins Biology Adenocarcinoma Metastasis Mice Cell Line Tumor Genetics medicine Animals Humans Lung cancer Molecular Biology Adaptor Proteins Signal Transducing Gene knockdown Mice Inbred BALB C Microfilament Proteins Lewis lung carcinoma Membrane Proteins YAP-Signaling Proteins medicine.disease Phosphoproteins Angiomotin Gene Expression Regulation Neoplastic Mice Inbred C57BL Cell Transformation Neoplastic HEK293 Cells Angiomotins Tumor progression CYR61 Immunology Cancer research Disease Progression Intercellular Signaling Peptides and Proteins Tumor promotion Acyltransferases Cysteine-Rich Protein 61 Protein Binding Transcription Factors |
| Zdroj: | Oncogene. 34(31) |
| ISSN: | 1476-5594 |
| Popis: | Lung cancer is the leading cause of cancer death worldwide, with metastasis underlying majority of related deaths. Angiomotin (AMOT), a scaffold protein, has been shown to interact with oncogenic Yes-associated protein/transcriptional co-activator with a PDZ-binding motif (YAP/TAZ) proteins, suggesting a potential role in tumor progression. However, the functional role of AMOT in lung cancer remains unknown. This study aimed to identify the patho-physiological characteristics of AMOT in lung cancer progression. Results revealed that AMOT expression was significantly decreased in clinical lung cancer specimens. Knockdown of AMOT in a low metastatic CL1-0 lung cancer cell line initiated cancer proliferation, migration, invasion and epithelial-mesenchymal transition. The trigger of cancer progression caused by AMOT loss was transduced by decreased cytoplasmic sequestration and increased nuclear translocation of oncogenic co-activators YAP/TAZ, leading to increased expression of the growth factor, Cyr61. Tumor promotion by AMOT knockdown was reversed when YAP/TAZ or Cyr61 was absent. Further, AMOT knockdown increased the growth and spread of Lewis lung carcinoma in vivo. These findings suggest that AMOT is a crucial suppressor of lung cancer metastasis and highlight its critical role as a tumor suppressor and its potential as a prognostic biomarker and therapeutic target for lung cancer. |
| Databáze: | OpenAIRE |
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