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.
authors.affiliation: New Drug Targets Laboratory, School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 500-712, Republic of Korea.
authors.forename: Da-Woon
authors.initials: DW
authors.lastname: Jung
authors.forename: Jinmi
authors.initials: J
authors.lastname: Kim
authors.forename: Zhong Min
authors.initials: ZM
authors.lastname: Che
authors.forename: Eun-Sang
authors.initials: ES
authors.lastname: Oh
authors.forename: Gicheon
authors.initials: G
authors.lastname: Kim
authors.forename: Soo Hyun
authors.initials: SH
authors.lastname: Eom
authors.forename: Sin-Hyeog
authors.initials: SH
authors.lastname: Im
authors.forename: Hyung-Ho
authors.initials: HH
authors.lastname: Ha
authors.forename: Young-Tae
authors.initials: YT
authors.lastname: Chang
authors.forename: Darren R
authors.initials: DR
authors.lastname: Williams
authors.forename: Jin
authors.initials: J
authors.lastname: Kim
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology; D002450:Cell Communication / Q000187:drug effects*; D002460:Cell Line; D002465:Cell Movement; D018925:Chemokines / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009062:Mouth Neoplasms / Q000378:metabolism / Q000473:pathology; D011485:Protein Binding; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D014183:Transplantation, Heterologous; D014227:Triazines / Q000737:chemistry / Q000494:pharmacology*; D015027:Zebrafish
chemical_list: D000970:Antineoplastic Agents; D018925:Chemokines; D018841:HSP90 Heat-Shock Proteins; D034741:RNA, Small Interfering; D014227:Triazines