TY - JOUR T1 - Oncogenic MST1R Activity in Pancreatic and Gastric Cancer Represents a Valid Target of HSP90 Inhibitors JF - Anticancer Research JO - Anticancer Res SP - 427 LP - 437 VL - 32 IS - 2 AU - CHRISTIAN MOSER AU - SVEN A. LANG AU - CHRISTINA HACKL AU - HONG ZHANG AU - KAREN LUNDGREN AU - VICTOR HONG AU - ANDRES MCKENZIE AU - BERNHARD WEBER AU - JUNG S. PARK AU - HANS J. SCHLITT AU - EDWARD K. GEISSLER AU - YOUNG D. JUNG AU - OLIVER STOELTZING Y1 - 2012/02/01 UR - http://ar.iiarjournals.org/content/32/2/427.abstract N2 - Aim: To evaluate the effects of HSP90 blockade by EC154 on the oncogenic receptor tyrosine kinase macrophage-stimulating 1 receptor (MST1R) in gastric and pancreatic cancer. Materials and Methods: Impact of EC154 on signaling pathways was investigated by western blotting. Cancer cell migration was evaluated in Boyden chambers. Transcriptional regulation of MST1R was examined by using promoter-luciferase reporter constructs. Effects on MST1R expression, and tumor growth were investigated in in vivo tumor models. Results: MST1R was expressed by cancer cells without evidence of MST1R mutations. EC154 led to an effective inhibition of cancer cell growth, down-regulated MST1R, diminished its promoter activity, and disrupted oncogenic macrophage-stimulating protein 1 (MSP1) signaling. Moreover, pro-migratory activities of cancer cells were dramatically inhibited. In vivo, treatment with EC154 significantly reduced tumor growth, while MST1R expression was down-regulated. Conclusion: Wild-type MST1R is an HSP90 client protein that can be targeted in gastrointestinal cancer using HSP90 inhibitors. ER -