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10.1186/s12929-018-0432-6

http://scihub22266oqcxt.onion/10.1186/s12929-018-0432-6
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suck abstract from ncbi


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pmid29592811      J+Biomed+Sci 2018 ; 25 (ä): ä
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  • Novel microtubule inhibitor MPT0B098 inhibits hypoxia-induced epithelial-to-mesenchymal transition in head and neck squamous cell carcinoma #MMPMID29592811
  • Tsai IT; Kuo CC; Liou JP; Chang JY
  • J Biomed Sci 2018[]; 25 (ä): ä PMID29592811show ga
  • Background: Tumor hypoxia-induced epithelial?mesenchymal transition (EMT) is critical in promoting cancer metastasis. We recently discovered a novel microtubule inhibitor, MPT0B098, that employs a novel antitumor mechanism. It destabilizes hypoxia-inducible factor (HIF)-1? mRNA by blocking the function of human antigen R. Thus, we proposed that MPT0B098 modulates hypoxia-induced EMT. Methods: In vitro IC50 values were determined through the methylene blue dye assay. To investigate molecular events, reverse transcriptase-polymerase chain reaction, Western blotting, immunofluorescence staining, and wound healing assay were employed. Results: MPT0B098 significantly inhibited HIF-1? expression, epithelial-to-mesenchymal morphology changes, and migratory ability in the human head and neck squamous cell carcinoma cell line OEC-M1. Furthermore, after MPT0B098 treatment, the expression of two mesenchymal markers, vimentin and N-cadherin, was downregulated under hypoxic conditions. Moreover, MPT0B098 suppressed hypoxia-induced EMT in part by inhibiting EMT-activating transcription factors, Twist and SNAI2/Slug. In addition, the inhibition of hypoxia-induced F-actin rearrangement and focal adhesion kinase phosphorylation may have contributed to suppression of EMT by MPT0B098in OEC-M1 cells. MPT0B098 significantly inhibited transforming growth factor(TGF)-?-induced phosphorylation of receptor-associated Smad2/3 by downregulating TGF-? mRNA and protein expression. Conclusions: Taken together, this study provides a novel insight into the role of MPT0B098 in inhibiting hypoxia-induced EMT, suggesting its potential use for treating head and neck cancers. Electronic supplementary material: The online version of this article (10.1186/s12929-018-0432-6) contains supplementary material, which is available to authorized users.
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