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

Authors
 Da-Woon Jung  ;  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  ;  Jin Kim 
Citation
 CHEMISTRY & BIOLOGY , Vol.18(12) : 1581-1590, 2011 
Journal Title
CHEMISTRY & BIOLOGY
ISSN
 1074-5521 
Issue Date
2011
MeSH
Animals ; Antineoplastic Agents/pharmacology ; Carcinoma, Squamous Cell/metabolism ; Carcinoma, Squamous Cell/pathology ; Cell Communication/drug effects* ; Cell Line ; Cell Movement ; Chemokines/metabolism ; Fibroblasts/metabolism ; HSP90 Heat-Shock Proteins/antagonists & inhibitors ; HSP90 Heat-Shock Proteins/genetics ; HSP90 Heat-Shock Proteins/metabolism* ; Humans ; Mouth Neoplasms/metabolism ; Mouth Neoplasms/pathology ; Protein Binding ; RNA Interference ; RNA, Small Interfering/metabolism ; Transplantation, Heterologous ; Triazines/chemistry ; Triazines/pharmacology* ; Zebrafish
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.
Full Text
http://www.sciencedirect.com/science/article/pii/S1074552111003607
DOI
10.1016/j.chembiol.2011.10.001
Appears in Collections:
2. College of Dentistry (치과대학) > Dept. of Oral Pathology (구강병리학교실) > 1. Journal Papers
Yonsei Authors
Kim, Jin(김진)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/94933
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