Inhibition of the MET Kinase Activity and Cell Growth in MET-Addicted Cancer Cells by Bi-Paratopic Linking.

Andres F, Iamele L, Meyer T, Stuber JC, Kast F, Gherardi E, Niemann H, Pluckthun A (2019)
Journal of molecular biology.

Download
Es wurde kein Volltext hochgeladen. Nur Publikationsnachweis!
Zeitschriftenaufsatz | E-Veröff. vor dem Druck | Englisch
Autor
; ; ; ; ; ; ;
Abstract / Bemerkung
MET, the product of the c-MET proto-oncogene, and its ligand hepatocyte growth factor/scatter factor (HGF/SF) control survival, proliferation and migration during development and tissue regeneration. HGF/SF-MET signaling is equally crucial for growth and metastasis of a variety of human tumors but resistance to small-molecule inhibitors of MET kinase develops rapidly and therapeutic antibody targeting remains challenging. We made use of the designed ankyrin repeat protein (DARPin) technology to develop an alternative approach for inhibiting MET. We generated a collection of MET-binding DARPins covering epitopes in the extracellular MET domains and created comprehensive sets of bi-paratopic fusion proteins. This new class of molecules efficiently inhibited MET kinase activity and downstream signaling, caused receptor downregulation and strongly inhibited the proliferation of MET-dependent gastric carcinoma cells carrying MET locus amplifications. MET-specific bi-paratopic DARPins may represent a novel and potent strategy for therapeutic targeting of MET and other receptors, and this study has elucidated their mode of action. Copyright © 2019. Published by Elsevier Ltd.
Erscheinungsjahr
Zeitschriftentitel
Journal of molecular biology
eISSN
PUB-ID

Zitieren

Andres F, Iamele L, Meyer T, et al. Inhibition of the MET Kinase Activity and Cell Growth in MET-Addicted Cancer Cells by Bi-Paratopic Linking. Journal of molecular biology. 2019.
Andres, F., Iamele, L., Meyer, T., Stuber, J. C., Kast, F., Gherardi, E., Niemann, H., et al. (2019). Inhibition of the MET Kinase Activity and Cell Growth in MET-Addicted Cancer Cells by Bi-Paratopic Linking. Journal of molecular biology. doi:10.1016/j.jmb.2019.03.024
Andres, F., Iamele, L., Meyer, T., Stuber, J. C., Kast, F., Gherardi, E., Niemann, H., and Pluckthun, A. (2019). Inhibition of the MET Kinase Activity and Cell Growth in MET-Addicted Cancer Cells by Bi-Paratopic Linking. Journal of molecular biology.
Andres, F., et al., 2019. Inhibition of the MET Kinase Activity and Cell Growth in MET-Addicted Cancer Cells by Bi-Paratopic Linking. Journal of molecular biology.
F. Andres, et al., “Inhibition of the MET Kinase Activity and Cell Growth in MET-Addicted Cancer Cells by Bi-Paratopic Linking.”, Journal of molecular biology, 2019.
Andres, F., Iamele, L., Meyer, T., Stuber, J.C., Kast, F., Gherardi, E., Niemann, H., Pluckthun, A.: Inhibition of the MET Kinase Activity and Cell Growth in MET-Addicted Cancer Cells by Bi-Paratopic Linking. Journal of molecular biology. (2019).
Andres, Fabio, Iamele, Luisa, Meyer, Timo, Stuber, Jakob C, Kast, Florian, Gherardi, Ermanno, Niemann, Hartmut, and Pluckthun, Andreas. “Inhibition of the MET Kinase Activity and Cell Growth in MET-Addicted Cancer Cells by Bi-Paratopic Linking.”. Journal of molecular biology (2019).

Export

Markieren/ Markierung löschen
Markierte Publikationen

Open Data PUB

Web of Science

Dieser Datensatz im Web of Science®

Quellen

PMID: 30930049
PubMed | Europe PMC

Suchen in

Google Scholar