A triazine compound S06 inhibits proinvasive crosstalk between carcinoma cells and stromal fibroblasts via binding to heat shock protein 90

Da Woon Jung, Jin Kim, Jinmi Kim, Zhong Min Che, Eun Sang Oh, Gicheon Kim, Soo Hyun Eom, Sin Hyeog Im, Hyung Ho Ha, Young Tae Chang, Darren R. Williams

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Carcinoma-associated fibroblasts (CAFs) promote tumor invasion by secreting soluble factors. A tagged triazine library was screened in our novel transwell coculture model of CAF and oral squamous cell carcinoma (OSCC). We discovered compound S06, which reduced OSCC invasion by inhibiting secretion of CAF-derived proinvasive chemokines. The N-terminus of Hsp90 was found to be the cellular target of S06. Importantly, S06 did not induce hepatic toxicity, a side effect associated with well-known Hsp90 inhibitors. Moreover, S06 inhibited tumor cell migration in a zebrafish xenograft model. Our results demonstrate that Hsp90 is a novel target for stromal-based therapy to modulate proinvasive molecular crosstalk within the tumor microenvironment. Furthermore, S06 represents a new class of Hsp90 inhibitor and is an attractive candidate for anticancer drug development.

Original languageEnglish
Pages (from-to)1581-1590
Number of pages10
JournalChemistry and Biology
Volume18
Issue number12
DOIs
Publication statusPublished - 2011 Dec 23

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Drug Discovery
  • Clinical Biochemistry

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    Jung, D. W., Kim, J., Kim, J., Che, Z. M., Oh, E. S., Kim, G., Eom, S. H., Im, S. H., Ha, H. H., Chang, Y. T., & Williams, D. R. (2011). A triazine compound S06 inhibits proinvasive crosstalk between carcinoma cells and stromal fibroblasts via binding to heat shock protein 90. Chemistry and Biology, 18(12), 1581-1590. https://doi.org/10.1016/j.chembiol.2011.10.001