Single cell profiling of potentiated phospho-protein networks in cancer cells.

Irish JM, Hovland R, Krutzik PO, Perez OD, Bruserud Ø, Gjertsen BT, Nolan GP
Cell. 2004 118 (2): 217-28

PMID: 15260991 · DOI:10.1016/j.cell.2004.06.028

Altered growth factor responses in phospho-protein-driven signaling networks are crucial to cancer cell survival and pathology. Profiles of cancer cell signaling networks might therefore identify mechanisms by which such cells interpret environmental cues for continued growth. Using multiparameter flow cytometry, we monitored phospho-protein responses to environmental cues in acute myeloid leukemia at the single cell level. By exposing cancer cell signaling networks to potentiating inputs, rather than relying upon the basal levels of protein phosphorylation alone, we could discern unique cancer network profiles that correlated with genetics and disease outcome. Strikingly, individual cancers manifested multiple cell subsets with unique network profiles, reflecting cancer heterogeneity at the level of signaling response. The results revealed a dramatic remodeling of signaling networks in cancer cells. Thus, single cell measurements of phospho-protein responses reveal shifts in signaling potential of a phospho-protein network, allowing for categorizing of cell network phenotypes by multidimensional molecular profiles of signaling.

MeSH Terms (20)

Antineoplastic Agents Carcinogens, Environmental Cell Transformation, Neoplastic DNA-Binding Proteins Flow Cytometry Fluorescent Antibody Technique fms-Like Tyrosine Kinase 3 Gene Expression Regulation, Neoplastic Humans Leukemia, Myeloid, Acute MAP Kinase Signaling System Mutation Phosphoproteins Phosphorylation Proto-Oncogene Proteins ras Proteins Receptor Protein-Tyrosine Kinases Signal Transduction STAT1 Transcription Factor Trans-Activators

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