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Emerging Roles of DLK1 in the Stem Cell Niche and Cancer Stemness

Grassi, Elisa Stellaria, Pietras, Alexander·2022·Journal of Histochemistry & Cytochemistry
DOI 10.1369/00221554211048951PMC PMC8721543
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Abstract

DLK1 is a maternally imprinted, paternally expressed gene coding for the transmembrane protein Delta-like homologue 1 (DLK1), a non-canonical NOTCH ligand with well-described roles during development, and tumor-supportive functions in several aggressive cancer forms. Here, we review the many functions of DLK1 as a regulator of stem cell pools and tissue differentiation in tissues such as brain, muscle, and liver. Furthermore, we review recent evidence supporting roles for DLK1 in the maintenance of aggressive stem cell characteristics of tumor cells, specifically focusing on central nervous system tumors, neuroblastoma, and hepatocellular carcinoma. We discuss NOTCH -dependent as well as NOTCH-independent functions of DLK1, and focus particularly on the complex pattern of DLK1 expression and cleavage that is finely regulated from a spatial and temporal perspective. Progress in recent years suggest differential functions of extracellular, soluble DLK1 as a paracrine stem cell niche-secreted factor, and has revealed a role for the intracellular domain of DLK1 in cell signaling and tumor stemness. A better understanding of DLK1 regulation and signaling may enable therapeutic targeting of cancer stemness by interfering with DLK1 release and/or intracellular signaling.

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  • RNA-seq of hippocampal tissues from middle-aged mice treated with TAC for 3 weeks induced a significant increase in expression of genes positively associated with adult hippocampus neurogenesis and brain function, including Eomes, Dlk1, Gdnf, Dcx, Sox1/2, Gdf11, and Fos.

    “Remarkably, TAC treatment induced a significant increase in the expression of genes positively associated with adult hippocampus neurogenesis and brain function,30–35 including Eomes, a driver of immune cell development & neurogenesis, Dlk1, a mediator of adult hippocampal neurogenesis and cognition, Gdnf, a neurotrophic factor, Dcx, a marker for new-born neurons, Sox1/2, critical determinants of”

    From TERT activation targets DNA methylation and multiple aging hallmarks (2024) · cites this paper as [34]

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Metadata

Authors
Grassi, E. S., & Pietras, A.
Affiliations
  • Department of Medical Biotechnology and Translational Medicine, University of Milan, Milan, Italy
  • Division of Translational Cancer Research, Department of Laboratory Medicine, Lund University, Lund, Sweden
Venue
Journal of Histochemistry & Cytochemistry
Publisher
SAGE Publications
Published
2021-10-04
Volume
70
Issue
1
Pages
17-28
ISSN
  • 0022-1554
  • 1551-5044
DOI
10.1369/00221554211048951
PMC
PMC8721543
Cited by
55
References
4
Language
en
Licence
creativecommons.org/licenses/by/4.0/ (unspecified)

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