ACADL-YAP axis activity in non-small cell lung cancer carcinogenicity
Abstract Background The role of Acyl-CoA dehydrogenase long chain (ACADL) in different tumor types had different inhibiting or promoting effect. However, its role in non-small cell lung cancer (NSCLC) carcinogenicity is not clear. Method In this study, we utilized The Cancer Genome Atlas (TCGA) data...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2024-02-01
|
| Series: | Cancer Cell International |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12935-024-03276-7 |
| _version_ | 1797273198751907840 |
|---|---|
| author | Kegong Chen Chunqiao Hong Weibo Kong Guanghua Li Zhuang Liu Kechao Zhu Chen Lu Panpan Si Pan Gao Guangyao Ning Renquan Zhang |
| author_facet | Kegong Chen Chunqiao Hong Weibo Kong Guanghua Li Zhuang Liu Kechao Zhu Chen Lu Panpan Si Pan Gao Guangyao Ning Renquan Zhang |
| author_sort | Kegong Chen |
| collection | DOAJ |
| description | Abstract Background The role of Acyl-CoA dehydrogenase long chain (ACADL) in different tumor types had different inhibiting or promoting effect. However, its role in non-small cell lung cancer (NSCLC) carcinogenicity is not clear. Method In this study, we utilized The Cancer Genome Atlas (TCGA) database to analyze ACADL expression in NSCLC and its correlation with overall survival. Furthermore, we investigated the function of ACADL on cellular proliferation, invasion, colony, apoptosis, cell cycle in vitro with NSCLC cells. Mechanistically, we evaluated the regulatory effect of ACADL expression on its downstream factor yes-associated protein (YAP) by assessing YAP phosphorylation levels and its cellular localization. Finally, we verified the tumorigenic effect of ACADL on NSCLC cells through xenograft experiments in vivo. Results Compared to adjacent non-cancerous samples, ACADL significantly down-regulated in NSCLC. Overexpression of ACADL, effectively reduced the proliferative, colony, and invasive capabilities of NSCLC cells, while promoting apoptosis and inducing cell cycle arrest. Moreover, ACADL overexpression significantly enhanced YAP phosphorylation and hindered its nuclear translocation. However, the inhibitory effect of the overexpression of ACADL in NSCLC cells mentioned above can be partially counteracted by YAP activator XMU-MP-1 application both in vitro and in vivo. Conclusion The findings suggest that ACADL overexpression could suppress NSCLC development by modulating YAP phosphorylation and limiting its nuclear shift. This role of ACADL-YAP axis provided novel insights into NSCLC carcinogenicity and potential therapeutic strategies. |
| first_indexed | 2024-03-07T14:40:08Z |
| format | Article |
| id | doaj.art-caba9a735cd642a8b2092ab79e180910 |
| institution | Directory Open Access Journal |
| issn | 1475-2867 |
| language | English |
| last_indexed | 2024-03-07T14:40:08Z |
| publishDate | 2024-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Cancer Cell International |
| spelling | doaj.art-caba9a735cd642a8b2092ab79e1809102024-03-05T20:25:35ZengBMCCancer Cell International1475-28672024-02-0124111410.1186/s12935-024-03276-7ACADL-YAP axis activity in non-small cell lung cancer carcinogenicityKegong Chen0Chunqiao Hong1Weibo Kong2Guanghua Li3Zhuang Liu4Kechao Zhu5Chen Lu6Panpan Si7Pan Gao8Guangyao Ning9Renquan Zhang10Department of Thoracic Surgery, The First Affiliated Hospital of Anhui Medical UniversityDepartment of Critical Care Medicine, Xiamen Chang Gung Hospital Hua Qiao UniversityDepartment of Thoracic Surgery, The First Affiliated Hospital of Anhui Medical UniversityDepartment of Thoracic Surgery, The Second Affiliated Hospital of Harbin Medical UniversityDepartment of Cardiovascular Surgery, The First Affiliated Hospital of Anhui Medical UniversityDepartment of Thoracic Surgery, The First Affiliated Hospital of Anhui Medical UniversityDepartment of Thoracic Surgery, The First Affiliated Hospital of Anhui Medical UniversityDepartment of Thoracic Surgery, The First Affiliated Hospital of Anhui Medical UniversityDepartment of Urology, The First Affiliated Hospital of Anhui Medical UniversityDepartment of Thoracic Surgery, The First Affiliated Hospital of Anhui Medical UniversityDepartment of Thoracic Surgery, The First Affiliated Hospital of Anhui Medical UniversityAbstract Background The role of Acyl-CoA dehydrogenase long chain (ACADL) in different tumor types had different inhibiting or promoting effect. However, its role in non-small cell lung cancer (NSCLC) carcinogenicity is not clear. Method In this study, we utilized The Cancer Genome Atlas (TCGA) database to analyze ACADL expression in NSCLC and its correlation with overall survival. Furthermore, we investigated the function of ACADL on cellular proliferation, invasion, colony, apoptosis, cell cycle in vitro with NSCLC cells. Mechanistically, we evaluated the regulatory effect of ACADL expression on its downstream factor yes-associated protein (YAP) by assessing YAP phosphorylation levels and its cellular localization. Finally, we verified the tumorigenic effect of ACADL on NSCLC cells through xenograft experiments in vivo. Results Compared to adjacent non-cancerous samples, ACADL significantly down-regulated in NSCLC. Overexpression of ACADL, effectively reduced the proliferative, colony, and invasive capabilities of NSCLC cells, while promoting apoptosis and inducing cell cycle arrest. Moreover, ACADL overexpression significantly enhanced YAP phosphorylation and hindered its nuclear translocation. However, the inhibitory effect of the overexpression of ACADL in NSCLC cells mentioned above can be partially counteracted by YAP activator XMU-MP-1 application both in vitro and in vivo. Conclusion The findings suggest that ACADL overexpression could suppress NSCLC development by modulating YAP phosphorylation and limiting its nuclear shift. This role of ACADL-YAP axis provided novel insights into NSCLC carcinogenicity and potential therapeutic strategies.https://doi.org/10.1186/s12935-024-03276-7Non-small cell lung cancerNuclear transferPhosphorylationYAPACADL |
| spellingShingle | Kegong Chen Chunqiao Hong Weibo Kong Guanghua Li Zhuang Liu Kechao Zhu Chen Lu Panpan Si Pan Gao Guangyao Ning Renquan Zhang ACADL-YAP axis activity in non-small cell lung cancer carcinogenicity Cancer Cell International Non-small cell lung cancer Nuclear transfer Phosphorylation YAP ACADL |
| title | ACADL-YAP axis activity in non-small cell lung cancer carcinogenicity |
| title_full | ACADL-YAP axis activity in non-small cell lung cancer carcinogenicity |
| title_fullStr | ACADL-YAP axis activity in non-small cell lung cancer carcinogenicity |
| title_full_unstemmed | ACADL-YAP axis activity in non-small cell lung cancer carcinogenicity |
| title_short | ACADL-YAP axis activity in non-small cell lung cancer carcinogenicity |
| title_sort | acadl yap axis activity in non small cell lung cancer carcinogenicity |
| topic | Non-small cell lung cancer Nuclear transfer Phosphorylation YAP ACADL |
| url | https://doi.org/10.1186/s12935-024-03276-7 |
| work_keys_str_mv | AT kegongchen acadlyapaxisactivityinnonsmallcelllungcancercarcinogenicity AT chunqiaohong acadlyapaxisactivityinnonsmallcelllungcancercarcinogenicity AT weibokong acadlyapaxisactivityinnonsmallcelllungcancercarcinogenicity AT guanghuali acadlyapaxisactivityinnonsmallcelllungcancercarcinogenicity AT zhuangliu acadlyapaxisactivityinnonsmallcelllungcancercarcinogenicity AT kechaozhu acadlyapaxisactivityinnonsmallcelllungcancercarcinogenicity AT chenlu acadlyapaxisactivityinnonsmallcelllungcancercarcinogenicity AT panpansi acadlyapaxisactivityinnonsmallcelllungcancercarcinogenicity AT pangao acadlyapaxisactivityinnonsmallcelllungcancercarcinogenicity AT guangyaoning acadlyapaxisactivityinnonsmallcelllungcancercarcinogenicity AT renquanzhang acadlyapaxisactivityinnonsmallcelllungcancercarcinogenicity |