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

IF 16.4 1区化学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Accounts of Chemical Research Pub Date : 2022-01-01 Epub Date: 2021-10-04 DOI:10.1369/00221554211048951

Elisa Stellaria Grassi, Alexander Pietras

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引用次数: 10

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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DLK1在干细胞生态位和癌症干细胞性中的新作用。

DLK1是一种母体印迹、父亲表达的基因，编码跨膜蛋白δ样同源物1 (DLK1)，这是一种非规范的NOTCH配体，在发育过程中具有良好的作用，并在几种侵袭性癌症中具有肿瘤支持功能。在这里，我们回顾了DLK1作为脑、肌肉和肝脏等组织中干细胞池和组织分化的调节因子的许多功能。此外，我们回顾了最近支持DLK1在维持肿瘤细胞侵袭性干细胞特征中的作用的证据，特别是集中在中枢神经系统肿瘤、神经母细胞瘤和肝细胞癌中。我们讨论了DLK1依赖NOTCH和不依赖NOTCH的功能，并特别关注DLK1表达和切割的复杂模式，从空间和时间的角度进行了精细调节。近年来的进展表明，细胞外可溶性DLK1作为旁分泌干细胞壁龛分泌因子具有不同的功能，并揭示了细胞内DLK1在细胞信号传导和肿瘤干性中的作用。更好地了解DLK1的调控和信号传导，可以通过干扰DLK1的释放和/或细胞内信号传导，实现癌症干细胞的靶向治疗。

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来源期刊

Accounts of Chemical Research 化学-化学综合

CiteScore

31.40

自引率

1.10%

发文量

312

审稿时长

2 months

期刊介绍： Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.