ArticleInflammatory intestinal diseases2018
Eribulin Does Not Prevent Epithelial-to-Mesenchymal Transition in HT-29 Intestinal Epithelial Cells.
Article in Inflammatory intestinal diseases, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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2 citing papers in PubMed, 2 citations in OpenAlex.
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
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Abstract
backgroundFistula formation affects up to 50$ of Crohn's disease (CD) patients and causes considerable morbidity. Current pharmacological management mainly includes antibiotics, immunosuppressives, and anti-TNF antibodies. CD fistulas develop from intestinal epithelial cells undergoing epithelial-to-mesenchymal transition (EMT). TGFβ, the most important inducer of EMT, is detectable around CD fistula tracts and induces expression of the EMT-associated transcription factors SNAIL1 and SLUG as well as of IL-13. Conversely, together with TNF, IL-13 induces the expression of the transcription factor Ets-1 and β6-integrin, which are associated with cell invasiveness. Eribulin is a synthetic derivative of halichondrin B, a large polyether macrolide, which reverses EMT in triple-negative breast cancer (TNBC) cells. Here, we investigated whether Eribulin might be a potential therapeutic option for CD fistulas via the inhibition of EMT. SUMMARY: Chronic treatment with high concentrations of Eribulin (> 5 ng/ml) is toxic for intestinal epithelial cells (IEC), and Eribulin treatment does not decrease the mRNA expression of EMT markers in HT-29 monolayers nor prevent EMT in HT-29 spheroids. Together with TNF, Eribulin induces the expression of vimentin and SLUG mRNA in HT-29 spheroids but concomitantly also promotes E-cadherin expression. KEY MESSAGES: Our data suggest that the previously reported antimetastatic effect of Eribulin in TNBC by reversing EMT does not apply to IEC. Interestingly, Eribulin promotes E-cadherin expression, suggesting an additional mechanism. The increase of E-cadherin might point towards the described role for Eribulin in reversing EMT. Taken together, our data do not support a role for Eribulin as treatment option for CD-associated fistulas.
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