Reversine inhibits Colon Carcinoma Cell Migration by Targeting JNK1.
Mohamed JemaàYasmin AbassiChamseddine KifagiMyriam FezaiRenée DaamsFlorian LangRamin MassoumiPublished in: Scientific reports (2018)
Colorectal cancer is one of the most commonly diagnosed cancers and the third most common cause of cancer-related death. Metastasis is the leading reason for the resultant mortality of these patients. Accordingly, development and characterization of novel anti-cancer drugs limiting colorectal tumor cell dissemination and metastasis are needed. In this study, we found that the small molecule Reversine reduces the migration potential of human colon carcinoma cells in vitro. A coupled kinase assay with bio-informatics approach identified the c-Jun N-terminal kinase (JNK) cascade as the main pathway inhibited by Reversine. Knockdown experiments and pharmacological inhibition identified JNK1 but not JNK2, as a downstream effector target in cancer cell migration. Xenograft experiments confirm the effect of JNK inhibition in the metastatic potential of colon cancer cells. These results highlight the impact of individual JNK isoforms in cancer cell metastasis and propose Reversine as a novel anti-cancer molecule for treatment of colon cancer patients.
Keyphrases
- cell migration
- signaling pathway
- cell death
- induced apoptosis
- small molecule
- end stage renal disease
- small cell lung cancer
- squamous cell carcinoma
- chronic kidney disease
- endothelial cells
- ejection fraction
- endoplasmic reticulum stress
- newly diagnosed
- high throughput
- single cell
- peritoneal dialysis
- regulatory t cells
- coronary artery disease
- prognostic factors
- patient reported outcomes
- risk factors
- young adults
- dendritic cells
- electronic health record
- climate change
- deep learning
- big data