TY - JOUR A1 - Harwardt, Marie-Lena I. E. A1 - Schröder, Mark S. A1 - Li, Yunqing A1 - Malkusch, Sebastian A1 - Freund, Petra A1 - Gupta, Shashi A1 - Janjic, Nebojsa A1 - Strauss, Sebastian A1 - Jungmann, Ralf A1 - Dietz, Marina A1 - Heilemann, Mike T1 - Single-molecule super-resolution microscopy reveals heteromeric complexes of MET and EGFR upon ligand activation T2 - International journal of molecular sciences N2 - 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 KW - receptor tyrosine kinases KW - MET KW - EGFR KW - receptor cross-interaction KW - single-molecule localization microscopy KW - single-particle tracking KW - DNA-PAINT Y1 - 2020 UR - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/55320 UR - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-553206 SN - 1422-0067 SN - 1661-6596 N1 - This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). VL - 21 IS - 8, art. 2803 SP - 1 EP - 20 PB - MDPI CY - Basel ER -