Ergotamine Targets KIF5A to Facilitate Anoikis in Lung Adenocarcinoma
ABSTRACT Background Kinesin family member 5A (KIF5A) has been reported to be closely related to cancer progression. The aim of this study was to investigate the effect of KIF5A on lung adenocarcinoma (LUAD) and its potential molecular mechanisms. Methods Using bioinformatics analysis methods and mol...
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Wiley
2024-11-01
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| Series: | The Clinical Respiratory Journal |
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| Online Access: | https://doi.org/10.1111/crj.70020 |
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| author | Bin Bao Xiaojun Yu Wujun Zheng Jiewei Sun |
| author_facet | Bin Bao Xiaojun Yu Wujun Zheng Jiewei Sun |
| author_sort | Bin Bao |
| collection | DOAJ |
| description | ABSTRACT Background Kinesin family member 5A (KIF5A) has been reported to be closely related to cancer progression. The aim of this study was to investigate the effect of KIF5A on lung adenocarcinoma (LUAD) and its potential molecular mechanisms. Methods Using bioinformatics analysis methods and molecular experiments, the expression of KIF5A in LUAD was analyzed, with its expression in attached and detached tumor cells assessed. Gene set enrichment analysis (GSEA) of KIF5A was carried out. The small molecular drug with the highest affinity for KIF5A was screened out through molecular docking experiments, which was validated through cellular thermal shift assay (CETSA). Quantitative polymerase chain reaction (qPCR) was employed to measure the expression levels of anoikis‐repressing genes (BCL2, CAV1), as well as anoikis‐inducing gene (PDCD4). CCK‐8 assay was applied to examine cell viability. Cell colony formation experiments were utilized to evaluate cell proliferation ability. Results We observed that KIF5A was highly upregulated in LUAD tissues and cells, with a higher level detected in detached LUAD cells. By resorting to bioinformatics analysis, we discovered that KIF5A was abundant in the anoikis pathway. Knocking down KIF5A reinforced anoikis in LUAD. Further screening identified Ergotamine as the small molecular drug with the highest affinity for KIF5A. The CETSA confirmed the binding relationship between the two. In addition, Ergotamine has a promoting effect on the anoikis of LUAD, while overexpression of KIF5A reversed the effects of Ergotamine on LUAD cells. Conclusion This project uncovered that the small molecular drug Ergotamine targets and inhibits the expression of KIF5A. Downregulated KIF5A can enhance the anoikis of LUAD. Our results supported the inhibition of KIF5A as an attractive therapeutic strategy for LUAD. This finding provides a new innovative pathway for the treatment of LUAD and offers a strong theoretical basis for the development of therapeutic drugs targeting KIF5A. |
| format | Article |
| id | doaj-art-95e7cd1592d44404a0fbaaf23d800b26 |
| institution | OA Journals |
| issn | 1752-6981 1752-699X |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Wiley |
| record_format | Article |
| series | The Clinical Respiratory Journal |
| spelling | doaj-art-95e7cd1592d44404a0fbaaf23d800b262025-08-20T02:23:31ZengWileyThe Clinical Respiratory Journal1752-69811752-699X2024-11-011811n/an/a10.1111/crj.70020Ergotamine Targets KIF5A to Facilitate Anoikis in Lung AdenocarcinomaBin Bao0Xiaojun Yu1Wujun Zheng2Jiewei Sun3Cardiothoracic Surgery Department The First People's Hospital of Fuyang Hangzhou ChinaCardiothoracic Surgery Department The First People's Hospital of Fuyang Hangzhou ChinaCardiothoracic Surgery Department The First People's Hospital of Fuyang Hangzhou ChinaCardiothoracic Surgery Department The First People's Hospital of Fuyang Hangzhou ChinaABSTRACT Background Kinesin family member 5A (KIF5A) has been reported to be closely related to cancer progression. The aim of this study was to investigate the effect of KIF5A on lung adenocarcinoma (LUAD) and its potential molecular mechanisms. Methods Using bioinformatics analysis methods and molecular experiments, the expression of KIF5A in LUAD was analyzed, with its expression in attached and detached tumor cells assessed. Gene set enrichment analysis (GSEA) of KIF5A was carried out. The small molecular drug with the highest affinity for KIF5A was screened out through molecular docking experiments, which was validated through cellular thermal shift assay (CETSA). Quantitative polymerase chain reaction (qPCR) was employed to measure the expression levels of anoikis‐repressing genes (BCL2, CAV1), as well as anoikis‐inducing gene (PDCD4). CCK‐8 assay was applied to examine cell viability. Cell colony formation experiments were utilized to evaluate cell proliferation ability. Results We observed that KIF5A was highly upregulated in LUAD tissues and cells, with a higher level detected in detached LUAD cells. By resorting to bioinformatics analysis, we discovered that KIF5A was abundant in the anoikis pathway. Knocking down KIF5A reinforced anoikis in LUAD. Further screening identified Ergotamine as the small molecular drug with the highest affinity for KIF5A. The CETSA confirmed the binding relationship between the two. In addition, Ergotamine has a promoting effect on the anoikis of LUAD, while overexpression of KIF5A reversed the effects of Ergotamine on LUAD cells. Conclusion This project uncovered that the small molecular drug Ergotamine targets and inhibits the expression of KIF5A. Downregulated KIF5A can enhance the anoikis of LUAD. Our results supported the inhibition of KIF5A as an attractive therapeutic strategy for LUAD. This finding provides a new innovative pathway for the treatment of LUAD and offers a strong theoretical basis for the development of therapeutic drugs targeting KIF5A.https://doi.org/10.1111/crj.70020anoikisErgotaminekinesin family member 5Alung adenocarcinoma |
| spellingShingle | Bin Bao Xiaojun Yu Wujun Zheng Jiewei Sun Ergotamine Targets KIF5A to Facilitate Anoikis in Lung Adenocarcinoma The Clinical Respiratory Journal anoikis Ergotamine kinesin family member 5A lung adenocarcinoma |
| title | Ergotamine Targets KIF5A to Facilitate Anoikis in Lung Adenocarcinoma |
| title_full | Ergotamine Targets KIF5A to Facilitate Anoikis in Lung Adenocarcinoma |
| title_fullStr | Ergotamine Targets KIF5A to Facilitate Anoikis in Lung Adenocarcinoma |
| title_full_unstemmed | Ergotamine Targets KIF5A to Facilitate Anoikis in Lung Adenocarcinoma |
| title_short | Ergotamine Targets KIF5A to Facilitate Anoikis in Lung Adenocarcinoma |
| title_sort | ergotamine targets kif5a to facilitate anoikis in lung adenocarcinoma |
| topic | anoikis Ergotamine kinesin family member 5A lung adenocarcinoma |
| url | https://doi.org/10.1111/crj.70020 |
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