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Lindner AU, Salvucci M, McDonough E, et al. An atlas of inter- and intra-tumor heterogeneity of apoptosis competency in colorectal cancer tissue at single-cell resolution. Cell Death Differ. 2021;doi: 10.1038/s41418-021-00895-9.
Lindner, A. U., Salvucci, M., McDonough, E., Cho, S., Stachtea, X., O'Connell, E. P., Corwin, A. D., Santamaria-Pang, A., Carberry, S., Fichtner, M., Van Schaeybroeck, S., Laurent-Puig, P., Burke, J. P., McNamara, D. A., Lawler, M., Sood, A., Graf, J. F., Rehm, M., Dunne, P. D., Longley, D. B., Ginty, F., & Prehn, J. H. M. (2021). An atlas of inter- and intra-tumor heterogeneity of apoptosis competency in colorectal cancer tissue at single-cell resolution. Cell death and differentiation, . https://doi.org/10.1038/s41418-021-00895-9
Lindner, Andreas Ulrich, et al. "An atlas of inter- and intra-tumor heterogeneity of apoptosis competency in colorectal cancer tissue at single-cell resolution." Cell death and differentiation vol. (2021). doi: https://doi.org/10.1038/s41418-021-00895-9
Lindner AU, Salvucci M, McDonough E, Cho S, Stachtea X, O'Connell EP, Corwin AD, Santamaria-Pang A, Carberry S, Fichtner M, Van Schaeybroeck S, Laurent-Puig P, Burke JP, McNamara DA, Lawler M, Sood A, Graf JF, Rehm M, Dunne PD, Longley DB, Ginty F, Prehn JHM. An atlas of inter- and intra-tumor heterogeneity of apoptosis competency in colorectal cancer tissue at single-cell resolution. Cell Death Differ. 2021 Nov 09; doi: 10.1038/s41418-021-00895-9. Epub 2021 Nov 09. PMID: 34754079.
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Cell Death Differ. 2021 Nov 09; doi: 10.1038/s41418-021-00895-9. Epub 2021 Nov 09.

An atlas of inter- and intra-tumor heterogeneity of apoptosis competency in colorectal cancer tissue at single-cell resolution.

Cell death and differentiation

Andreas Ulrich Lindner, Manuela Salvucci, Elizabeth McDonough, Sanghee Cho, Xanthi Stachtea, Emer P O'Connell, Alex D Corwin, Alberto Santamaria-Pang, Steven Carberry, Michael Fichtner, Sandra Van Schaeybroeck, Pierre Laurent-Puig, John P Burke, Deborah A McNamara, Mark Lawler, Anup Sood, John F Graf, Markus Rehm, Philip D Dunne, Daniel B Longley, Fiona Ginty, Jochen H M Prehn

Affiliations

  1. Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland University of Medicine and Health Sciences, 123 St. Stephen's Green, Dublin 2, Ireland.
  2. Centre of Systems Medicine, Royal College of Surgeons in Ireland University of Medicine and Health Sciences, 123 St. Stephen's Green, Dublin 2, Ireland.
  3. GE Research, Niskayuna, NY, 12309, USA.
  4. Centre for Cancer Research & Cell Biology, Queen's University Belfast, 97 Lisburn Road, Belfast, BT9 7AE, Northern Ireland, UK.
  5. Department of Surgery, Royal College of Surgeons in Ireland University of Medicine and Health Sciences, 123 St. Stephen's Green, Dublin 2, Ireland.
  6. Centre de Recherche des Cordeliers, INSERM, CNRS, Université de Paris, Sorbonne Université, USPC, Equipe labellisée Ligue Nationale Contre le Cancer, Paris, France.
  7. Beaumont Hospital, Beaumont Road, Dublin 9, Ireland.
  8. Institute of Cell Biology and Immunology, University of Stuttgart, Allmandring 31, 70569, Stuttgart, Germany.
  9. Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland University of Medicine and Health Sciences, 123 St. Stephen's Green, Dublin 2, Ireland. [email protected].
  10. Centre of Systems Medicine, Royal College of Surgeons in Ireland University of Medicine and Health Sciences, 123 St. Stephen's Green, Dublin 2, Ireland. [email protected].

PMID: 34754079 DOI: 10.1038/s41418-021-00895-9

Abstract

Cancer cells' ability to inhibit apoptosis is key to malignant transformation and limits response to therapy. Here, we performed multiplexed immunofluorescence analysis on tissue microarrays with 373 cores from 168 patients, segmentation of 2.4 million individual cells, and quantification of 18 cell lineage and apoptosis proteins. We identified an enrichment for BCL2 in immune, and BAK, SMAC, and XIAP in cancer cells. Ordinary differential equation-based modeling of apoptosis sensitivity at single-cell resolution was conducted and an atlas of inter- and intra-tumor heterogeneity in apoptosis susceptibility generated. Systems modeling at single-cell resolution identified an enhanced sensitivity of cancer cells to mitochondrial permeabilization and executioner caspase activation compared to immune and stromal cells, but showed significant inter- and intra-tumor heterogeneity.

© 2021. The Author(s).

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