Surface Immobilization of Redox-Labile Fluorescent Probes Enables Single-Cell Co-Profiling of Aerobic Glycolysis and Oncogenic Protein Signaling Activities.
Angew Chem Int Ed Engl. 2018 Jul 10;:
Authors: Li Z, Cheng H, Shao S, Lu X, Li M, Tsang J, Zeng P, Guo Z, Wang S, Nathanson DA, Heath JR, Wei W, Xue M
We describe an analytical method for profiling lactate production in single cells, via the use of coupled enzyme reactions on surface-grafted resazurin molecules. The immobilization of the redox-labile probes was achieved through chemical modifications on resazurin, followed by bio-orthogonal click reactions. The lactate detection scheme was demonstrated to be sensitive and specific. The method was incorporated into the single cell barcode chip platform for simultaneous quantification of aerobic glycolysis activities and oncogenic signaling phosphoproteins in cancer. We interrogated the interplay between glycolysis and oncogenic signaling activities on a glioblastoma cell line. Results revealed a drug-induced oncogenic signaling reliance accompanying shifted metabolic paradigms. A drug combination that exploits this induced reliance exhibited synergistic effects in growth inhibition.
PMID: 29992724 [PubMed – as supplied by publisher]