Single-Cell Chemical Proteomics (SCCP) Interrogates the Timing and Heterogeneity of Cancer Cell Commitment to Death

Chemical proteomics
studies the effects of drugs upon a cellular
proteome. Due to the complexity and diversity of tumors, the response
of cancer cells to drugs is also heterogeneous, and thus, proteome
analysis at the single-cell level is needed. Here, we demonstrate
that single-cell proteomics techniques have become quantitative enough
to tackle the drug effects on target proteins, enabling single-cell
chemical proteomics (SCCP). Using SCCP, we studied here the time-resolved
response of individual adenocarcinoma A549 cells to anticancer drugs
methotrexate, camptothecin, and tomudex, revealing the early emergence
of cellular subpopulations committed and uncommitted to death. As
a novel and useful approach to exploring the heterogeneous response
to drugs of cancer cells, SCCP may prove to be a breakthrough application
for single-cell proteomics.