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Journal article

Reversine inhibits Colon Carcinoma Cell Migration by Targeting JNK1

From

Lund University1

National Veterinary Institute, Technical University of Denmark2

Mucosal Immunology, Division of Immunology & Vaccinology, National Veterinary Institute, Technical University of Denmark3

University of Tübingen4

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.

Language: English
Publisher: Nature Publishing Group UK
Year: 2018
Pages: 11821
ISSN: 20452322
Types: Journal article
DOI: 10.1038/s41598-018-30251-w
ORCIDs: 0000-0003-4905-1020 and 0000-0003-2962-1540

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