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

doi:10.1016/j.chembiol.2011.10.001

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

Department of Oral Pathology

Research output: Contribution to journal › Article › peer-review

18 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 language	English
Pages (from-to)	1581-1590
Number of pages	10
Journal	Chemistry and Biology
Volume	18
Issue number	12
DOIs	https://doi.org/10.1016/j.chembiol.2011.10.001
Publication status	Published - 2011 Dec 23

Bibliographical note

Funding Information:
This research was supported by a grant from the National Research Foundation funded by the Korean government (MEST basic science research program NRF-2009-0067894 to D.-W.J.) and a grant from the Priority Research Centers Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2010-0029702 to J.K.). We also acknowledge the Bioimaging Research Center, Gwangju Institute of Science and Technology, for provision of microscopy facilities.

All Science Journal Classification (ASJC) codes

Biochemistry
Molecular Medicine
Molecular Biology
Pharmacology
Drug Discovery
Clinical Biochemistry

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10.1016/j.chembiol.2011.10.001

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

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.",

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

note = "Funding Information: This research was supported by a grant from the National Research Foundation funded by the Korean government (MEST basic science research program NRF-2009-0067894 to D.-W.J.) and a grant from the Priority Research Centers Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2010-0029702 to J.K.). We also acknowledge the Bioimaging Research Center, Gwangju Institute of Science and Technology, for provision of microscopy facilities. ",

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doi = "10.1016/j.chembiol.2011.10.001",

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AU - Jung, Da Woon

AU - Kim, Jin

AU - Kim, Jinmi

AU - Che, Zhong Min

AU - Oh, Eun Sang

AU - Kim, Gicheon

AU - Eom, Soo Hyun

AU - Im, Sin Hyeog

AU - Ha, Hyung Ho

AU - Chang, Young Tae

AU - Williams, Darren R.

N1 - Funding Information: This research was supported by a grant from the National Research Foundation funded by the Korean government (MEST basic science research program NRF-2009-0067894 to D.-W.J.) and a grant from the Priority Research Centers Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2010-0029702 to J.K.). We also acknowledge the Bioimaging Research Center, Gwangju Institute of Science and Technology, for provision of microscopy facilities.

PY - 2011/12/23

Y1 - 2011/12/23

N2 - 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.

AB - 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.

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

Abstract

Bibliographical note

All Science Journal Classification (ASJC) codes

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