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
Li, Zhonghan; Cheng, Hanjun; Shao, Shiqun; Lu, Xiang; Mo, Li; Tsang, Jonathan; Zeng, Pu; Guo, Zhili; Wang, Siwen; Nathanson, David A; Heath, James R; Wei, Wei; and Xue, Min, "Surface Immobilization of Redox-Labile Fluorescent Probes: Enabling Single-Cell Co-Profiling of Aerobic Glycolysis and Oncogenic Protein Signaling Activities." (2018). Articles, Abstracts, and Reports. 2015.