DOI: 10.5061/dryad.2280gb653
title: The kinase ERK plays a conserved dominant role in the heterogeneity of epithelial-mesenchymal transition in pancreatic cancer cells

description: Epithelial-mesenchymal transition (EMT) occurs heterogeneously among
 malignant carcinoma cells to promote chemoresistance. Identifying the
 signaling pathways involved will nominate drug combinations to promote
 chemoresponse, but cell population-level studies are inherently fraught,
 and single-cell transcriptomics are limited to indirect ontology-based
 inferences. To understand EMT heterogeneity at a signaling protein level,
 we combined iterative indirect immunofluorescence imaging of pancreas
 cancer cells and tumors and mutual information (MI) analysis. Focusing
 first on MAP kinase pathways, MI indicated that cell-to-cell variation in
 ERK activity dominated control of EMT heterogeneity in response to diverse
 growth factors and chemotherapeutics, but that JNK compensated when MEK
 was inhibited. Population-level models could not capture these
 experimentally validated MI inferences. The dominant role of ERK was
 persistently indicated by MI even when analyzing seven potential
 EMT-regulating signaling nodes. More generally, this work provides an
 approach for studying multivariate signaling/phenotype relationships based
 on protein measurements in any setting.
description: # The kinase ERK plays a conserved dominant role in the heterogeneity of
 epithelial-mesenchymal transition in pancreatic cancer cells Dataset DOI:
 [10.5061/dryad.2280gb653](10.5061/dryad.2280gb653) ## Description of the
 data and file structure Fluorescence intensity measurements from
 CellProfiler analysis of iterative indirect immunofluorescence imaging
 experiments measuring pathway activation proxies and cell phenotype
 markers. These data are used for mutual information analysis in our
 manuscript "The kinase ERK plays a conserved dominant role in the
 heterogeneity of epithelial-mesenchymal transition in pancreatic cancer
 cells." Each row is one object (cell) that was measured. Similar
 files ending in \_Cell, \_Cytoplasm, \_Nuclei, etc., can be merged using
 the Image and Object numbers from the dataset. *VIP variables:* *
 ImageNumber: Unique identifier for each image processed in the pipeline. *
 ObjectNumber: Unique identifier for each object found in the associated
 image. * Metadata_Well: Well number associated with a specific treatment
 condition, detailed in the experiment README files. *
 Intensity_IntegratedIntensity_{Target}: Total intensity of all of the
 pixels in the area of the segmented object for a given immunofluorescence
 image (arbitrary intensity units) * Example:
 Intensity_Integrated_Intensity_Vimentin ### Files and variables #### File:
 HPAF_growth_factor_panel_days1to5.zip **Description:** Data associated
 with Figure 1. Files: 1. Days1to5_GFs_Plate1_Cell.csv 2.
 Days1to5_GFs_Plate1_Cytoplasm.csv 3. Days1to5_GFs_Plate1_Nuclei.csv 4.
 Days1to5_GFs_Plate2_Cell.csv 5. Days1to5_GFs_Plate2_Cytoplasm.csv 6.
 Days1to5_GFs_Plate2_Nuclei.csv 7. README_HPAF_growth_factor_panel_days1to5
 #### File: KPCY_7160_cells_growth_factors_chemo.zip **Description:** Data
 associated with Figure 2 Files: 1. 7160_4i_Nuclei.csv 2. 7160_4i_Cell.csv
 3. 7160_4i_Cytoplasm.csv 4.
 README_KPCY_derived_7160_growth_factors_gemcitabine #### File:
 PDX395_cells_baseline_chemo.zip **Description:** Data associated with
 Figure 2 Files: 1. PDX395_cells_chemo_Nuclei.csv 2.
 PDX395_cells_chemo_Cell.csv 3. PDX395_cells_chemo_image_qc.csv 4.
 README_PDX_395_baseline_chemo_inhibitors #### File:
 HPAF_growth_factors_chemotherapy_7pathway_panel.zip **Description:** Data
 associated with Figure 6 Files: 1. Full_panel_4i_Nuclei.csv 2.
 Full_panel_4i_Cell.csv 3. Full_panel_4i_Cytoplasm.csv 4.
 Full_panel_4i_image_qc.csv 5.
 README_HPAF_full_pathway_panel_chemo_growth_factor #### File: PDX395.zip
 **Description:**  Data associated with Figure 7 Files: 1.
 395full_Nuclei.csv 2. 395full_Ecad.csv 3. 395full_Cytoplasm.csv 4.
 Pilot_395_Z_Mesmr_Nuclei.csv 5. Pilot_395_Z_Mesmr_Ecad.csv 6.
 Pilot_395_Z_Mesmr_Cytoplasm.csv 7. README_PDX_395 ## Code/software Code
 for analysis available on Zenodo:
 [https://doi.org/10.5281/zenodo.16042277](https://doi.org/10.5281/zenodo.16042277) ## Access information Other publicly accessible locations of the data: * Data also available through the University of Virginia Dataverse: [https://doi.org/10.18130/V3/KJCIGC](https://doi.org/10.18130/V3/KJCIGC)