DLK1, delta-like 1 homolog (Drosophila), regulates tumor cell differentiation in vivo

Asma Begum, Yuri Kim, Qun Lin, Zhong Yun

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

The stem cell-like characteristics of tumor cells are not only essential for tumor development and malignant progression, but also significantly contribute to therapy resistance. However, it remains poorly understood how cancer cell differentiation or stemness is regulated in vivo. We investigated the role of the stem cell gene DLK1, or delta-like 1 homolog (Drosophila), in the regulation of cancer cell differentiation in vivo using neuroblastoma (NB) xenografts as a model. We found that loss-of-function mutants of DLK1 significantly enhanced NB cell differentiation in vivo likely by increasing the basal phosphorylation of MEK and ERK kinases, a mechanism that has been shown to facilitate neuronal differentiation. We also found that DLK1 + cells are preferentially located in hypoxic regions. These results clearly demonstrate that DLK1 plays an important role in the maintenance of undifferentiated, stem cell-like phenotypes of NB cells in vivo.

Original languageEnglish
Pages (from-to)26-33
Number of pages8
JournalCancer Letters
Volume318
Issue number1
DOIs
StatePublished - 1 May 2012

Bibliographical note

Funding Information:
We thank Dr. Nai-Kong V. Cheung of Memorial Sloan-Kettering Cancer Center for SK-N-ER cells, Dr. Robert Ross of Fordham University for BE(2)C cells, Dr. Ravi Bhatia of City of Hope National Medical Center for full-length DLK1 and DLK1-ΔCyto. We would like to thank Amos A. Brooks (Research Histology Laboratory, Department of Pathology, Yale School of Medicine) for the IHC staining and Lisa Cabral for her excellent editorial assistance. This work was supported by a grant from the National Institutes of Health to ZY (R01CA125021). However, the granting agency had no other involvement in the study.

Keywords

  • Cancer stem cell
  • DLK1
  • Differentiation
  • Hypoxia
  • Neuroblastoma

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