ReferenceID 4922
The small molecule chemical compound cinobufotalin attenuates resistance to DDP by inducing ENKUR expression to suppress MYH9-mediated c-Myc deubiquitination in lung adenocarcinoma
Acta Pharmacol Sin
The small molecule chemical compound cinobufotalin (CB) is reported to be a potential antitumour drug that increases cisplatin (DDP) sensitivity in nasopharyngeal carcinoma. In this study, we first found that CB decrease
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Record Fields
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- Reference Id
- 4922
- Evidence Id
- 21512
- Core Evidence Id
- 21512
- Source Reference Id
- 3100
- Herb2 Reference Id
- HBREF003897
- Subject Paper Key
- HBIN020703_35296779
- Pubmed Id
- 35296779
- Doi
- 10.1038/s41401-022-00890-x
- Paper Title
- The small molecule chemical compound cinobufotalin attenuates resistance to DDP by inducing ENKUR expression to suppress MYH9-mediated c-Myc deubiquitination in lung adenocarcinoma
- Paper Abstract
- The small molecule chemical compound cinobufotalin (CB) is reported to be a potential antitumour drug that increases cisplatin (DDP) sensitivity in nasopharyngeal carcinoma. In this study, we first found that CB decreased DDP resistance, migration and invasion in lung adenocarcinoma (LUAD). Mechanistic studies showed that CB induced ENKUR expression by suppressing PI3K/AKT signalling to downregulate c-Jun, a negative transcription factor of ENKUR. Furthermore, ENKUR was shown to function as a tumour suppressor by binding to β-catenin to decrease c-Jun expression, thus suppressing MYH9 transcription. Interestingly, MYH9 is a binding protein of ENKUR. The Enkurin domain of ENKUR binds to MYH9, and the Myosin_tail of MYH9 binds to ENKUR. Downregulation of MYH9 reduced the recruitment of the deubiquitinase USP7, leading to increased c-Myc ubiquitination and degradation, decreased c-Myc nuclear translocation, and inactivation of epithelial-mesenchymal transition (EMT) signalling, thus attenuating DDP resistance. Our data demonstrated that CB is a promising antitumour drug and may be a candidate chemotherapeutic drug for LUAD patients.
- Journal
- Acta Pharmacol Sin
- Publish Year
- 2022
- Experiment Subject
- patient
- Experiment Type
- Cell Experiment
- Phenotype Related
- Lung Adenocarcinoma; Nasopharyngeal Carcinoma; Tumour
- Paper Title Cn
- Paper Title En
- The small molecule chemical compound cinobufotalin attenuates resistance to DDP by inducing ENKUR expression to suppress MYH9-mediated c-Myc deubiquitination in lung adenocarcinoma
- Bilingual Status
- semi_complete