Cul4A Modulates Invasion and Metastasis of Lung Cancer through Regulation of ANXA10
Cullin 4A (Cul4A) is overexpressed in a number of cancers and has been established as an oncogene. This study aimed to elucidate the role of Cul4A in lung cancer invasion and metastasis. We observed that Cul4A was overexpressed in non-small cell lung cancer (NSCLC) tissues and the overexpression of...
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| Language: | English |
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MDPI AG
2019-05-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/11/5/618 |
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| author | Ming-Szu Hung Yi-Chuan Chen Paul-Yann Lin Ya-Chin Li Chia-Chen Hsu Jr-Hau Lung Liang You Zhidong Xu Jian-Hua Mao David M. Jablons Cheng-Ta Yang |
| author_facet | Ming-Szu Hung Yi-Chuan Chen Paul-Yann Lin Ya-Chin Li Chia-Chen Hsu Jr-Hau Lung Liang You Zhidong Xu Jian-Hua Mao David M. Jablons Cheng-Ta Yang |
| author_sort | Ming-Szu Hung |
| collection | DOAJ |
| description | Cullin 4A (Cul4A) is overexpressed in a number of cancers and has been established as an oncogene. This study aimed to elucidate the role of Cul4A in lung cancer invasion and metastasis. We observed that Cul4A was overexpressed in non-small cell lung cancer (NSCLC) tissues and the overexpression of Cul4A was associated with poor prognosis after surgical resection and it also decreased the expression of the tumor suppressor protein annexin A10 (ANXA10). The knockdown of Cul4A was associated with the upregulation of ANXA10, and the forced expression of Cul4A was associated with the downregulation of ANXA10 in lung cancer cells. Further studies showed that the knockdown of Cul4A inhibited the invasion and metastasis of lung cancer cells, which was reversed by the further knockdown of ANXA10. In addition, the knockdown of Cul4A inhibited lung tumor metastasis in mouse tail vein injection xenograft models. Notably, Cul4A regulated the degradation of ANXA10 through its interaction with ANXA10 and ubiquitination in lung cancer cells. Our findings suggest that Cul4A is a prognostic marker in NSCLC patients, and Cul4A plays important roles in lung cancer invasion and metastasis through the regulation of the ANXA10 tumor suppressor. |
| first_indexed | 2024-03-12T20:02:40Z |
| format | Article |
| id | doaj.art-49be7c277cb04d05978b26099bbd6598 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-12T20:02:40Z |
| publishDate | 2019-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-49be7c277cb04d05978b26099bbd65982023-08-02T02:18:38ZengMDPI AGCancers2072-66942019-05-0111561810.3390/cancers11050618cancers11050618Cul4A Modulates Invasion and Metastasis of Lung Cancer through Regulation of ANXA10Ming-Szu Hung0Yi-Chuan Chen1Paul-Yann Lin2Ya-Chin Li3Chia-Chen Hsu4Jr-Hau Lung5Liang You6Zhidong Xu7Jian-Hua Mao8David M. Jablons9Cheng-Ta Yang10Division of Thoracic Oncology, Department of Pulmonary and Critical Care Medicine, Chang Gung Memorial Hospital, Chiayi branch 61363, TaiwanDepartment of Emergency Medicine, Chang Gung Memorial Hospital, Chiayi branch 61363, TaiwanDepartment of Anatomic Pathology, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi 62247, TaiwanDivision of Thoracic Oncology, Department of Pulmonary and Critical Care Medicine, Chang Gung Memorial Hospital, Chiayi branch 61363, TaiwanDepartment of Hematology and Oncology, Chang Gung Memorial Hospital, Chiayi branch 61363, TaiwanDepartment of Medical Research and Development, Chang Gung Memorial Hospital, Chiayi branch 61363, TaiwanThoracic Oncology Laboratory, Department of Surgery, Comprehensive Cancer Center, University of California, San Francisco, CA 94143, USAThoracic Oncology Laboratory, Department of Surgery, Comprehensive Cancer Center, University of California, San Francisco, CA 94143, USALife Sciences Division, Lawrence Berkeley National Laboratory, One Cyclotron Road, Berkeley, CA 94720, USAThoracic Oncology Laboratory, Department of Surgery, Comprehensive Cancer Center, University of California, San Francisco, CA 94143, USADepartment of Respiratory Care, College of Medicine, Chang Gung University, Taoyuan 33302, TaiwanCullin 4A (Cul4A) is overexpressed in a number of cancers and has been established as an oncogene. This study aimed to elucidate the role of Cul4A in lung cancer invasion and metastasis. We observed that Cul4A was overexpressed in non-small cell lung cancer (NSCLC) tissues and the overexpression of Cul4A was associated with poor prognosis after surgical resection and it also decreased the expression of the tumor suppressor protein annexin A10 (ANXA10). The knockdown of Cul4A was associated with the upregulation of ANXA10, and the forced expression of Cul4A was associated with the downregulation of ANXA10 in lung cancer cells. Further studies showed that the knockdown of Cul4A inhibited the invasion and metastasis of lung cancer cells, which was reversed by the further knockdown of ANXA10. In addition, the knockdown of Cul4A inhibited lung tumor metastasis in mouse tail vein injection xenograft models. Notably, Cul4A regulated the degradation of ANXA10 through its interaction with ANXA10 and ubiquitination in lung cancer cells. Our findings suggest that Cul4A is a prognostic marker in NSCLC patients, and Cul4A plays important roles in lung cancer invasion and metastasis through the regulation of the ANXA10 tumor suppressor.https://www.mdpi.com/2072-6694/11/5/618lung cancerCul4AANXA10metastasis |
| spellingShingle | Ming-Szu Hung Yi-Chuan Chen Paul-Yann Lin Ya-Chin Li Chia-Chen Hsu Jr-Hau Lung Liang You Zhidong Xu Jian-Hua Mao David M. Jablons Cheng-Ta Yang Cul4A Modulates Invasion and Metastasis of Lung Cancer through Regulation of ANXA10 Cancers lung cancer Cul4A ANXA10 metastasis |
| title | Cul4A Modulates Invasion and Metastasis of Lung Cancer through Regulation of ANXA10 |
| title_full | Cul4A Modulates Invasion and Metastasis of Lung Cancer through Regulation of ANXA10 |
| title_fullStr | Cul4A Modulates Invasion and Metastasis of Lung Cancer through Regulation of ANXA10 |
| title_full_unstemmed | Cul4A Modulates Invasion and Metastasis of Lung Cancer through Regulation of ANXA10 |
| title_short | Cul4A Modulates Invasion and Metastasis of Lung Cancer through Regulation of ANXA10 |
| title_sort | cul4a modulates invasion and metastasis of lung cancer through regulation of anxa10 |
| topic | lung cancer Cul4A ANXA10 metastasis |
| url | https://www.mdpi.com/2072-6694/11/5/618 |
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