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

Elisa Stellaria Grassi1, Alexander Pietras2

  • 1Department of Medical Biotechnology and Translational Medicine, University of Milan, Milan, Italy.

The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society
|October 4, 2021
PubMed

Insights

Delta-like homologue 1 (DLK1) regulates stem cells and tissue differentiation. Recent studies highlight its role in maintaining aggressive cancer stem cell characteristics, suggesting DLK1 as a therapeutic target.

Area of Science:

  • Developmental Biology
  • Cancer Stem Cell Biology
  • Molecular Signaling

Background:

  • Delta-like homologue 1 (DLK1) is a transmembrane protein and non-canonical NOTCH ligand involved in development.
  • DLK1 plays a role in regulating stem cell pools and tissue differentiation in various organs.
  • Emerging evidence implicates DLK1 in supporting aggressive tumor cell characteristics.

Purpose of the Study:

  • To review the diverse functions of DLK1 in development and cancer.
  • To explore DLK1's role in maintaining cancer stemness, particularly in CNS tumors, neuroblastoma, and hepatocellular carcinoma.
  • To discuss the NOTCH-dependent and independent signaling pathways regulated by DLK1.

Main Methods:

  • Literature review of studies on DLK1 function in development and cancer.
  • Analysis of DLK1 expression patterns, cleavage, and signaling mechanisms.
  • Examination of evidence for soluble and intracellular DLK1 functions.

Main Results:

  • DLK1 regulates stem cell pools and differentiation in tissues like the brain, muscle, and liver.
  • DLK1 contributes to the maintenance of aggressive stem cell traits in specific cancers.
  • Both extracellular soluble DLK1 and intracellular DLK1 signaling impact tumor stemness.

Conclusions:

  • DLK1 exhibits complex spatial and temporal regulation, including differential functions of its soluble and intracellular forms.
  • Understanding DLK1's regulation and signaling is crucial for targeting cancer stemness.
  • Interfering with DLK1 release or signaling presents a potential therapeutic strategy against cancer stem cells.
Keywords:
DLK1angiogenesiscancerglioblastomastem cellstemnesstissue differentiationtumor heterogeneitytumor immune infiltratetumor microenvironment

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