Abstract:
:Expression of the transcription factor FOXC2 is induced and necessary for successful epithelial-mesenchymal transition, a developmental program that when activated in cancer endows cells with metastatic potential and the properties of stem cells. As such, identifying agents that inhibit the growth of FOXC2-transformed cells represents an attractive approach to inhibit chemotherapy resistance and metastatic dissemination. From a high throughput synthetic lethal screen, we identified a small molecule, FiVe1, which selectively and irreversibly inhibits the growth of mesenchymally transformed breast cancer cells and soft tissue sarcomas of diverse histological subtypes. FiVe1 targets the intermediate filament and mesenchymal marker vimentin (VIM) in a mode which promotes VIM disorganization and phosphorylation during metaphase, ultimately leading to mitotic catastrophe, multinucleation, and the loss of stemness. These findings illustrate a previously undescribed mechanism for interrupting faithful mitotic progression and may ultimately inform the design of therapies for a broad range of mesenchymal cancers.
journal_name
Proc Natl Acad Sci U S Aauthors
Bollong MJ,Pietilä M,Pearson AD,Sarkar TR,Ahmad I,Soundararajan R,Lyssiotis CA,Mani SA,Schultz PG,Lairson LLdoi
10.1073/pnas.1716009114subject
Has Abstractpub_date
2017-11-14 00:00:00pages
E9903-E9912issue
46eissn
0027-8424issn
1091-6490pii
1716009114journal_volume
114pub_type
杂志文章abstract::Transmission electron microscope images were obtained of fractions of poly(1-tetradecene sulfone) and poly(cyclohexene sulfone) cast from very dilute solutions (0.007%, wt/vol) and rapidly freeze-dried on a mica surface. The samples were then vertically platinum-carbon (Pt-C) replicated with 9 +/- 0.3-A Pt-C and held ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
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abstract::Noniridescent coloration by the spongy keratin in parrot feather barbs has fascinated scientists. Nonetheless, its ultimate origin remains as yet unanswered, and a quantitative structural and optical description is still lacking. Here we report on structural and optical characterizations and numerical simulations of t...
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abstract::Ouabain-sensitive uncoupled Na+ efflux has been studied in human, pig, and rat red cells and in vesicles containing reconstituted kidney Na+/K+ pumps obtained from these same species. The red cells from the different species gave qualitatively similar results; the uncoupled Na+ efflux was 15-30% of the Na+/K+ exchange...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:2019-10-08 00:00:00