Patterns of basal signaling heterogeneity can distinguish cellular populations with different drug sensitivities.
Phenotypic heterogeneity has been widely observed in cellular populations. However, the extent to which heterogeneity contains biologically or clinically important information is not well understood. Here, we investigated whether patterns of basal signaling heterogeneity, in untreated cancer cell populations, could distinguish cellular populations with different drug sensitivities. We modeled cellular heterogeneity as a mixture of stereotyped signaling states, identified based on colocalization patterns of activated signaling molecules from microscopy images. We found that patterns of heterogeneity could be used to separate the most sensitive and resistant populations to paclitaxel within a set of H460 lung cancer clones and within the NCI-60 panel of cancer cell lines, but not for a set of less heterogeneous, immortalized noncancer human bronchial epithelial cell (HBEC) clones. Our results suggest that patterns of signaling heterogeneity, characterized as ensembles of a small number of distinct phenotypic states, can reveal functional differences among cellular populations.
Singh
Dinesh Kumar
DK
Department of Pharmacology, Green Center for Systems Biology, Simmons Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX 75390-9041, USA.
Ku
Chin-Jen
CJ
Wichaidit
Chonlarat
C
Steininger
Robert J
RJ
Wu
Lani F
LF
Altschuler
Steven J
SJ
D014408:Biomarkers, Tumor / Q000235:genetics; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D018740:Genetic Heterogeneity; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008856:Microscopy, Fluorescence; D015999:Multivariate Analysis; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D017239:Paclitaxel / Q000494:pharmacology; D015398:Signal Transduction / Q000235:genetics; D049490:Systems Biology
D014408:Biomarkers, Tumor; D047908:Intracellular Signaling Peptides and Proteins; D017239:Paclitaxel
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