1. The role of delta-like non-canonical Notch ligand 1 (DLK1) in cancer.
- Author
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Pittaway, James F. H., Lipsos, Constantinos, Mariniello, Katia, and Guasti, Leonardo
- Subjects
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NOTCH signaling pathway , *CANCER stem cells , *MEMBRANE proteins , *NOTCH proteins , *PROGENITOR cells - Abstract
Delta-like non-canonical Notch ligand 1 (DLK1) is a cleavable single-pass transmembrane protein and a member of the Notch/Delta/Serrate family. It is p aternally expressed and belongs to a group of imprinted genes located on chromosome band 14q32 in humans and 12qF1 in mice. DLK1 is expressed in many human tissu es during embryonic development but in adults expression is low and is mostly restr icted to (neuro)endocrine tissues and other immature stem/progenitor cells (notably hepatoblasts). However, DLK1 is expressed at a high frequency in many common malignancies (l iver, breast, brain, pancreas, colon and lung). More recently, high levels of expression have been identified in endocrine-related cancers such as ovarian and adrenocortical carcinoma. There is growing evidence that DLK1 expression in cancer is associated with worse prognosis and that DLK1 may be a marker of cancer stem cells. Although th e exact mechanism through which DLK1 functions is not fully understood, it is kno wn to maintain cells in an undifferentiated phenotype and has oncogenic properties. These effects are partly exacted through interaction with the Notch signalling pathway. In this review, we have detailed the functional role of DLK1 within physiology and malignancy and posited a mechanism for how it exacts its oncogenic effects. In describing the expression of DLK1 in cancer and in healthy tissue, we have highlighted the potent ial for its use both as a biomarker and as a potential therapeutic target. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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