Please use this identifier to cite or link to this item: https://doi.org/10.1016/j.chembiol.2011.10.001
Title: A triazine compound S06 inhibits proinvasive crosstalk between carcinoma cells and stromal fibroblasts via binding to heat shock protein 90
Authors: 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.
Issue Date: 23-Dec-2011
Citation: 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. (2011-12-23). 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. ScholarBank@NUS Repository. https://doi.org/10.1016/j.chembiol.2011.10.001
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. © 2011 Elsevier Ltd. All Rights Reserved.
Source Title: Chemistry and Biology
URI: http://scholarbank.nus.edu.sg/handle/10635/75499
ISSN: 10745521
DOI: 10.1016/j.chembiol.2011.10.001
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