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

Grassi, Elisa Stellaria LU and Pietras, Alexander LU (2022) In Journal of Histochemistry and Cytochemistry 70(1). p.17-28
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... (More)

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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author
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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
angiogenesis, cancer, DLK1, glioblastoma, stem cell, stemness, tissue differentiation, tumor heterogeneity, tumor immune infiltrate, tumor microenvironment
in
Journal of Histochemistry and Cytochemistry
volume
70
issue
1
pages
17 - 28
publisher
Histochemical Society
external identifiers
  • scopus:85116357067
  • pmid:34606325
ISSN
0022-1554
DOI
10.1369/00221554211048951
language
English
LU publication?
yes
additional info
Publisher Copyright: © The Author(s) 2021.
id
5620714c-9fef-4204-b711-e700ef9426a0
date added to LUP
2021-10-25 15:30:15
date last changed
2024-06-15 19:16:13
@article{5620714c-9fef-4204-b711-e700ef9426a0,
  abstract     = {{<p>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.</p>}},
  author       = {{Grassi, Elisa Stellaria and Pietras, Alexander}},
  issn         = {{0022-1554}},
  keywords     = {{angiogenesis; cancer; DLK1; glioblastoma; stem cell; stemness; tissue differentiation; tumor heterogeneity; tumor immune infiltrate; tumor microenvironment}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{17--28}},
  publisher    = {{Histochemical Society}},
  series       = {{Journal of Histochemistry and Cytochemistry}},
  title        = {{Emerging Roles of DLK1 in the Stem Cell Niche and Cancer Stemness}},
  url          = {{http://dx.doi.org/10.1369/00221554211048951}},
  doi          = {{10.1369/00221554211048951}},
  volume       = {{70}},
  year         = {{2022}},
}