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Reversine inhibits Colon Carcinoma Cell Migration by Targeting JNK1

Jemaà, Mohamed LU ; Abassi, Yasmin LU ; Kifagi, Chamseddine LU ; Fezai, Myriam ; Daams, Renée LU ; Lang, Florian and Massoumi, Ramin LU (2018) In Scientific Reports 8(1).
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... (More)

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.

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author
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Scientific Reports
volume
8
issue
1
article number
11821
publisher
Nature Publishing Group
external identifiers
  • scopus:85051242297
  • pmid:30087398
ISSN
2045-2322
DOI
10.1038/s41598-018-30251-w
language
English
LU publication?
yes
id
bd4f4b21-3040-4c9e-8159-208183653377
date added to LUP
2018-09-06 08:51:51
date last changed
2021-10-06 01:16:41
@article{bd4f4b21-3040-4c9e-8159-208183653377,
  abstract     = {<p>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.</p>},
  author       = {Jemaà, Mohamed and Abassi, Yasmin and Kifagi, Chamseddine and Fezai, Myriam and Daams, Renée and Lang, Florian and Massoumi, Ramin},
  issn         = {2045-2322},
  language     = {eng},
  month        = {12},
  number       = {1},
  publisher    = {Nature Publishing Group},
  series       = {Scientific Reports},
  title        = {Reversine inhibits Colon Carcinoma Cell Migration by Targeting JNK1},
  url          = {http://dx.doi.org/10.1038/s41598-018-30251-w},
  doi          = {10.1038/s41598-018-30251-w},
  volume       = {8},
  year         = {2018},
}