Reversine inhibits Colon Carcinoma Cell Migration by Targeting JNK1

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Abstract

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.

Detaljer

Författare
Enheter & grupper
Externa organisationer
  • University of Tübingen
  • Technical University of Denmark
  • Heinrich Heine University Düsseldorf
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Cancer och onkologi
  • Cell- och molekylärbiologi
Originalspråkengelska
Artikelnummer11821
TidskriftScientific Reports
Volym8
Utgivningsnummer1
StatusPublished - 2018 dec 1
PublikationskategoriForskning
Peer review utfördJa