RYBP Inhibits Progression and Metastasis of Lung Cancer by Suppressing EGFR Signaling and Epithelial-Mesenchymal Transition
Lung cancer (LC) is a common lethal malignancy with rapid progression and metastasis, and Ring1 and YY1 binding protein (RYBP) has been shown to suppress cell growth in human cancers. This study aimed to investigate the role of RYBP in LC progression and metastasis. In this study, a total of 149 LC...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2017-04-01
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| Series: | Translational Oncology |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1936523316301735 |
| _version_ | 1811269498617987072 |
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| author | Xiaoxiao Dinglin Lin Ding Qingjian Li Yuanbin Liu Jiexia Zhang Herui Yao |
| author_facet | Xiaoxiao Dinglin Lin Ding Qingjian Li Yuanbin Liu Jiexia Zhang Herui Yao |
| author_sort | Xiaoxiao Dinglin |
| collection | DOAJ |
| description | Lung cancer (LC) is a common lethal malignancy with rapid progression and metastasis, and Ring1 and YY1 binding protein (RYBP) has been shown to suppress cell growth in human cancers. This study aimed to investigate the role of RYBP in LC progression and metastasis. In this study, a total of 149 LC patients were recruited, and the clinical stage of their tumors, metastasis status, survival time, presence of epidermal growth factor receptor (EGFR) mutation, and RYBP expression levels were measured. RYBP silencing and overexpression were experimentally performed in LC cell lines and in nude mice, and the expressions of genes in EGFR-related signaling pathways and epithelial-mesenchymal transition (EMT) were detected. The results showed that RYBP was downregulated in LC compared with adjacent normal tissues, and low RYBP expression was associated with a more severe clinical stage, high mortality, high metastasis risk, and poor survival. Cell proliferation and xenograft growth were inhibited by RYBP overexpression, whereas proliferation and xenograft growth were accelerated by RYBP silencing. EGFR and phosphorylated-EGFR levels were upregulated when RYBP was silenced, whereas EGFR, p-EGFR, p-AKT, and p-ERK were downregulated when RYBP was overexpressed. Low RYBP expression was related to a high metastasis risk, and metastasized tumors showed low RYBP levels. Cell migration and invasion were promoted by silencing RYBP but were inhibited by overexpressed RYBP. In addition, the EMT marker vimentin showed diminished expression, and E-cadherin was promoted by the overexpression of RYBP. In conclusion, our data suggest that RYBP suppresses cell proliferation and LC progression by impeding the EGFR-ERK and EGFR-AKT signaling pathways and thereby inhibiting cell migration and invasion and LC metastasis through the suppression of EMT. |
| first_indexed | 2024-04-12T21:43:07Z |
| format | Article |
| id | doaj.art-43047f454b6645f68b0ed6d387e90136 |
| institution | Directory Open Access Journal |
| issn | 1936-5233 1944-7124 |
| language | English |
| last_indexed | 2024-04-12T21:43:07Z |
| publishDate | 2017-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Translational Oncology |
| spelling | doaj.art-43047f454b6645f68b0ed6d387e901362022-12-22T03:15:42ZengElsevierTranslational Oncology1936-52331944-71242017-04-0110228028710.1016/j.tranon.2017.01.004RYBP Inhibits Progression and Metastasis of Lung Cancer by Suppressing EGFR Signaling and Epithelial-Mesenchymal TransitionXiaoxiao Dinglin0Lin Ding1Qingjian Li2Yuanbin Liu3Jiexia Zhang4Herui Yao5Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangzhou, 510120, ChinaGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangzhou, 510120, ChinaGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangzhou, 510120, ChinaClinical Medical Research Center of National Respiratory DiseasesClinical Medical Research Center of National Respiratory DiseasesGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangzhou, 510120, ChinaLung cancer (LC) is a common lethal malignancy with rapid progression and metastasis, and Ring1 and YY1 binding protein (RYBP) has been shown to suppress cell growth in human cancers. This study aimed to investigate the role of RYBP in LC progression and metastasis. In this study, a total of 149 LC patients were recruited, and the clinical stage of their tumors, metastasis status, survival time, presence of epidermal growth factor receptor (EGFR) mutation, and RYBP expression levels were measured. RYBP silencing and overexpression were experimentally performed in LC cell lines and in nude mice, and the expressions of genes in EGFR-related signaling pathways and epithelial-mesenchymal transition (EMT) were detected. The results showed that RYBP was downregulated in LC compared with adjacent normal tissues, and low RYBP expression was associated with a more severe clinical stage, high mortality, high metastasis risk, and poor survival. Cell proliferation and xenograft growth were inhibited by RYBP overexpression, whereas proliferation and xenograft growth were accelerated by RYBP silencing. EGFR and phosphorylated-EGFR levels were upregulated when RYBP was silenced, whereas EGFR, p-EGFR, p-AKT, and p-ERK were downregulated when RYBP was overexpressed. Low RYBP expression was related to a high metastasis risk, and metastasized tumors showed low RYBP levels. Cell migration and invasion were promoted by silencing RYBP but were inhibited by overexpressed RYBP. In addition, the EMT marker vimentin showed diminished expression, and E-cadherin was promoted by the overexpression of RYBP. In conclusion, our data suggest that RYBP suppresses cell proliferation and LC progression by impeding the EGFR-ERK and EGFR-AKT signaling pathways and thereby inhibiting cell migration and invasion and LC metastasis through the suppression of EMT.http://www.sciencedirect.com/science/article/pii/S1936523316301735 |
| spellingShingle | Xiaoxiao Dinglin Lin Ding Qingjian Li Yuanbin Liu Jiexia Zhang Herui Yao RYBP Inhibits Progression and Metastasis of Lung Cancer by Suppressing EGFR Signaling and Epithelial-Mesenchymal Transition Translational Oncology |
| title | RYBP Inhibits Progression and Metastasis of Lung Cancer by Suppressing EGFR Signaling and Epithelial-Mesenchymal Transition |
| title_full | RYBP Inhibits Progression and Metastasis of Lung Cancer by Suppressing EGFR Signaling and Epithelial-Mesenchymal Transition |
| title_fullStr | RYBP Inhibits Progression and Metastasis of Lung Cancer by Suppressing EGFR Signaling and Epithelial-Mesenchymal Transition |
| title_full_unstemmed | RYBP Inhibits Progression and Metastasis of Lung Cancer by Suppressing EGFR Signaling and Epithelial-Mesenchymal Transition |
| title_short | RYBP Inhibits Progression and Metastasis of Lung Cancer by Suppressing EGFR Signaling and Epithelial-Mesenchymal Transition |
| title_sort | rybp inhibits progression and metastasis of lung cancer by suppressing egfr signaling and epithelial mesenchymal transition |
| url | http://www.sciencedirect.com/science/article/pii/S1936523316301735 |
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