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  Single-Molecule Super-Resolution Microscopy Reveals Heteromeric Complexes of MET and EGFR upon Ligand Activation

Harwardt, M.-L.-I.-E., Schröder, M. S., Li, Y., Malkusch, S., Freund, P., Gupta, S., et al. (2020). Single-Molecule Super-Resolution Microscopy Reveals Heteromeric Complexes of MET and EGFR upon Ligand Activation. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 21(8): 2803. doi:10.3390/ijms21082803.

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 Creators:
Harwardt, Marie-Lena I. E.1, Author
Schröder, Mark S.1, Author
Li, Yunqing1, Author
Malkusch, Sebastian1, Author
Freund, Petra1, Author
Gupta, Shashi1, Author
Janjic, Nebojsa1, Author
Strauss, Sebastian2, Author           
Jungmann, Ralf2, Author           
Dietz, Marina S.1, Author
Heilemann, Mike1, Author
Affiliations:
1external, ou_persistent22              
2Jungmann, Ralf / Molecular Imaging and Bionanotechnology, Max Planck Institute of Biochemistry, Max Planck Society, ou_2149679              

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Free keywords: GROWTH-FACTOR-RECEPTOR; CELL LUNG-CANCER; COLOCALIZATION ANALYSIS; ACQUIRED-RESISTANCE; CROSS-TALK; C-MET; MUTATIONS; GEFITINIBreceptor tyrosine kinases; MET; EGFR; receptor cross-interaction; single-molecule localization microscopy; single-particle tracking; DNA-PAINT;
 Abstract: Receptor tyrosine kinases (RTKs) orchestrate cell motility and differentiation. Deregulated RTKs may promote cancer and are prime targets for specific inhibitors. Increasing evidence indicates that resistance to inhibitor treatment involves receptor cross-interactions circumventing inhibition of one RTK by activating alternative signaling pathways. Here, we used single-molecule super-resolution microscopy to simultaneously visualize single MET and epidermal growth factor receptor (EGFR) clusters in two cancer cell lines, HeLa and BT-20, in fixed and living cells. We found heteromeric receptor clusters of EGFR and MET in both cell types, promoted by ligand activation. Single-protein tracking experiments in living cells revealed that both MET and EGFR respond to their cognate as well as non-cognate ligands by slower diffusion. In summary, for the first time, we present static as well as dynamic evidence of the presence of heteromeric clusters of MET and EGFR on the cell membrane that correlates with the relative surface expression levels of the two receptors.

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Language(s): eng - English
 Dates: 2020
 Publication Status: Published online
 Pages: 20
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: ISI: 000535565300145
DOI: 10.3390/ijms21082803
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Title: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Source Genre: Journal
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Publ. Info: ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND : MDPI
Pages: - Volume / Issue: 21 (8) Sequence Number: 2803 Start / End Page: - Identifier: -