Anti-cancer activity of the novel 2-hydroxydiarylamide derivatives IMD-0354 and KRT1853 through suppression of cancer cell invasion, proliferation, and survival mediated by TMPRSS4

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Title
Anti-cancer activity of the novel 2-hydroxydiarylamide derivatives IMD-0354 and KRT1853 through suppression of cancer cell invasion, proliferation, and survival mediated by TMPRSS4
Author(s)
Solbi Kim; Dongjoon Ko; Yunhee Lee; S Jang; Y Lee; I Y Lee; Semi Kim
Bibliographic Citation
Scientific Reports, vol. 9, pp. 10003-10003
Publication Year
2019
Abstract
Elevated expression of transmembrane serine protease 4 (TMPRSS4) correlates with poor prognosis in non-small cell lung cancer, gastric cancer, colorectal cancer, prostate cancer, and other cancer patients. Previously, we demonstrated that TMPRSS4 mediates tumor cell invasion, migration, proliferation, and metastasis. In addition, we reported novel 2-hydroxydiarylamide derivatives, IMD-0354 and KRT1853, as TMPRSS4 serine protease inhibitors. Here, we further evaluated the effects of the representative derivatives on TMPRSS4-mediated cellular function and signaling. IMD-0354 and KRT1853 inhibited cancer cell invasion, migration, and proliferation in TMPRSS4-expressing prostate, colon, and lung cancer cells. Both compounds suppressed TMPRSS4-mediated induction of Sp1/3, AP-1, and NF-κB transcription factors. Furthermore, TMPRSS4 promoted cancer cell survival and drug resistance, and both compounds enhanced anoikis sensitivity as well as reduced bcl-2 and survivin levels. Importantly, KRT1853 efficiently reduced tumor growth in prostate and colon cancer xenograft models. These results strongly recommend KRT1853 for further development as a novel anti-cancer agent.
ISSN
2045-2322
Publisher
Springer-Nature Pub Group
DOI
http://dx.doi.org/10.1038/s41598-019-46447-7
Type
Article
Appears in Collections:
Division of Biomedical Research > Immunotherapy Research Center > 1. Journal Articles
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