Endothelial Transdifferentiation of Tumor Cells Triggered by the Twist1-Jagged1-KLF4 Axis: Relationship between Cancer Stemness and Angiogenesis.

Abstract:

:Tumor hypoxia is associated with malignant biological phenotype including enhanced angiogenesis and metastasis. Hypoxia increases the expression of vascular endothelial cell growth factor (VEGF), which directly participates in angiogenesis by recruiting endothelial cells into hypoxic area and stimulating their proliferation, for increasing vascular density. Recent research in tumor biology has focused on the model in which tumor-derived endothelial cells arise from tumor stem-like cells, but the detailed mechanism is not clear. Twist1, an important regulator of epithelial-mesenchymal transition (EMT), has been shown to mediate tumor metastasis and induce tumor angiogenesis. Notch signaling has been demonstrated to be an important player in vascular development and tumor angiogenesis. KLF4 (Krüppel-like factor 4) is a factor commonly used for the generation of induced pluripotent stem (iPS) cells. KLF4 also plays an important role in the differentiation of endothelial cells. Although Twist1 is known as a master regulator of mesoderm development, it is unknown whether Twist1 could be involved in endothelial transdifferentiation of tumor-derived cells. This review focuses on the role of Twist1-Jagged1/Notch-KLF4 axis on tumor-derived endothelial transdifferentiation, tumorigenesis, metastasis, and cancer stemness.

journal_name

Stem Cells Int

journal_title

Stem cells international

authors

Chen HF,Wu KJ

doi

10.1155/2016/6439864

subject

Has Abstract

pub_date

2016-01-01 00:00:00

pages

6439864

eissn

1687-966X

issn

1687-9678

journal_volume

2016

pub_type

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