Premium
Surface Immobilization of Redox‐Labile Fluorescent Probes: Enabling Single‐Cell Co‐Profiling of Aerobic Glycolysis and Oncogenic Protein Signaling Activities
Author(s) -
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,
Xue Min
Publication year - 2018
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201803034
Subject(s) - resazurin , chemistry , redox , glycolysis , anaerobic glycolysis , cell , enzyme , cell signaling , biochemistry , cancer cell , signal transduction , cell culture , cell growth , microbiology and biotechnology , biophysics , biology , cancer , organic chemistry , genetics
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.