%0 Journal Article %A CHRISTIAN MOSER %A SVEN A. LANG %A CHRISTINA HACKL %A HONG ZHANG %A KAREN LUNDGREN %A VICTOR HONG %A ANDRES MCKENZIE %A BERNHARD WEBER %A JUNG S. PARK %A HANS J. SCHLITT %A EDWARD K. GEISSLER %A YOUNG D. JUNG %A OLIVER STOELTZING %T Oncogenic MST1R Activity in Pancreatic and Gastric Cancer Represents a Valid Target of HSP90 Inhibitors %D 2012 %J Anticancer Research %P 427-437 %V 32 %N 2 %X 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. %U https://ar.iiarjournals.org/content/anticanres/32/2/427.full.pdf