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Using CRISPR/Cas9 Gene Editing to Investigate the Oncogenic Activity of Mutant Calreticulin in Cytokine Dependent Hematopoietic Cells
10:21

Using CRISPR/Cas9 Gene Editing to Investigate the Oncogenic Activity of Mutant Calreticulin in Cytokine Dependent Hematopoietic Cells

Published on: January 5, 2018

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Programmed cell removal by calreticulin in tissue homeostasis and cancer

Mingye Feng1,2, Kristopher D Marjon3,4,5, Fangfang Zhu3,4,5

  • 1Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, CA, 94305, USA. mfeng@coh.org.

Nature Communications
|August 12, 2018
PubMed

Insights

Macrophages use secreted calreticulin (CRT) to label unwanted cells, like aging neutrophils and cancer cells, for removal. This process, crucial for programmed cell removal (PrCR), involves CRT binding to asialoglycans on target cells.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Mechanisms

Background:

  • Macrophage-mediated programmed cell removal (PrCR) is vital for eliminating unwanted cells.
  • The molecular mechanisms of target cell recognition by macrophages for PrCR remain unclear.

Purpose of the Study:

  • To elucidate the molecular mechanisms by which macrophages detect and recognize target cells for PrCR.
  • To identify the specific molecules involved in macrophage-mediated clearance of unwanted cells.

Main Methods:

  • Utilized models of tissue turnover, cancer immunosurveillance, and hematopoietic stem cells.
  • Investigated the role of secreted calreticulin (CRT) in labeling target cells.
  • Identified asialoglycans on target cells as binding sites for CRT.

Main Results:

  • Macrophages secrete calreticulin (CRT) to label aging neutrophils and living cancer cells for clearance.
  • CRT binds to asialoglycans on target cells, mediating their recognition and removal via PrCR.
  • The presence of CRT-binding sites on cancer cells correlated with patient prognosis in various malignancies.

Conclusions:

  • Revealed a general mechanism for target cell recognition by macrophages in PrCR.
  • Identified secreted CRT and target cell asialoglycans as key components of this recognition system.
  • This finding has implications for understanding cell clearance in both physiological and pathological conditions, including cancer.

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