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Nat Commun. 2014 Aug 22;5:4697. doi: 10.1038/ncomms5697.

Twist1 induces endothelial differentiation of tumour cells through the Jagged1-KLF4 axis.

Author information

1
Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei 112, Taiwan.
2
Taiwan Advance Biopharm (TABP), Inc., Xizhi City, New Taipei City 221, Taiwan.
3
Department of Dentistry, Taipei Mackay Memorial Hospital, Taipei 104, Taiwan.
4
1] Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei 112, Taiwan [2] Department of Surgery, Taipei Veterans General Hospital, Taipei 112, Taiwan.
5
Department of Physical Medicine and Rehabilitation, ChangGung Memorial Hospital, Keelung 204, Taiwan.
6
Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei 100, Taiwan.
7
1] Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei 112, Taiwan [2] Genome Research Center, National Yang-Ming University, Taipei 112, Taiwan [3] Research Center for Tumor Medical Science, China Medical University, Taichung 40402, Taiwan.

Abstract

The mechanisms controlling tumour-induced angiogenesis are presently not clear. In principle, angiogenesis can be achieved through the activation of endothelial cells in existing vessels or by transdifferentiation of tumour cells into endothelial cells. However, whether tumour cells can go through a prior epithelial-mesenchymal transition and further differentiate into endothelial cells remains unknown. Here we show that overexpression of Twist1, a transcriptional regulator that induces and promotes cancer metastasis, leads to endothelial differentiation in head and neck cancer (HNC) cells. Induction of Jagged1 expression by Twist1 is essential for Twist1-induced endothelial differentiation. The Jagged1/Notch signalling subsequently activates KLF4, inducing stem-like properties in HNC cells and conferring them with drug resistance. Our results indicate that the Twist1-Jagged1/KLF4 axis is essential both for transdifferentiation of tumour cells into endothelial cells and for chemoresistance acquisition.

PMID:
25146389
DOI:
10.1038/ncomms5697
[Indexed for MEDLINE]

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