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Angewandte Chemie (International ed. in English)


Biosensing Techniques; Cell Line, Tumor; Click Chemistry; Fluorescent Dyes; Glycolysis; Humans; Lactic Acid; Models, Molecular; Neoplasms; Oncogene Proteins; Oxidation-Reduction; Signal Transduction; Single-Cell Analysis; Spectrometry, Fluorescence


An analytical method is described 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 was demonstrated to be sensitive and specific. The method was incorporated into a single-cell barcode chip for simultaneous quantification of aerobic glycolysis activities and oncogenic signaling phosphoproteins in cancer. The interplay between glycolysis and oncogenic signaling activities was interrogated 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.


Institute for Systems Biology