Moser, Christian and Lang, Sven A. and Hackl, Christina and Zhang, Hong and Lundgren, Karen and Hong, Victor and Mckenzie, Andres and Weber, Bernhard and Park, Jung S. and Schlitt, Hans J. and Geissler, Edward K. and Jung, Young D. and Stoeltzing, Oliver (2012) Oncogenic MST1R Activity in Pancreatic and Gastric Cancer Represents a Valid Target of HSP90 Inhibitors. ANTICANCER RESEARCH, 32 (2). pp. 427-437. ISSN 0250-7005, 1791-7530
Full text not available from this repository. (Request a copy)Abstract
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 he targeted in gastrointestinal cancer using HSP90 inhibitors.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | RECEPTOR TYROSINE KINASE; MACROPHAGE-STIMULATING PROTEIN; ENDOTHELIAL GROWTH-FACTOR; MULTIFUNCTIONAL DOCKING SITE; RON RECEPTOR; POINT MUTATIONS; AUTOCRINE LOOP; CELL-MIGRATION; TUMOR-GROWTH; IN-VIVO; MST1R; HSP90; pancreatic cancer; gastric cancer; HPAF-II cells; L3,6 pl cells; TMK-1 cells |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Chirurgie Medicine > Lehrstuhl für Humangenetik |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 20 May 2020 05:11 |
| Last Modified: | 20 May 2020 05:11 |
| URI: | https://pred.uni-regensburg.de/id/eprint/19309 |
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