title: Twist1 induces endothelial differentiation of tumour cells through the Jagged1-KLF4 axis.
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.
authors.affiliation: Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei 112, Taiwan.
authors.forename: Hsiao-Fan
authors.initials: HF
authors.lastname: Chen
authors.affiliation: Taiwan Advance Biopharm (TABP), Inc., Xizhi City, New Taipei City 221, Taiwan.
authors.forename: Chi-Hung
authors.initials: CH
authors.lastname: Huang
authors.affiliation: Department of Dentistry, Taipei Mackay Memorial Hospital, Taipei 104, Taiwan.
authors.forename: Chung-Ji
authors.initials: CJ
authors.lastname: Liu
authors.affiliation: 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.
authors.forename: Jung-Jyh
authors.initials: JJ
authors.lastname: Hung
authors.affiliation: Department of Physical Medicine and Rehabilitation, ChangGung Memorial Hospital, Keelung 204, Taiwan.
authors.forename: Chih-Chin
authors.initials: CC
authors.lastname: Hsu
authors.affiliation: Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei 100, Taiwan.
authors.forename: Shu-Chun
authors.initials: SC
authors.lastname: Teng
authors.affiliation: 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.
authors.forename: Kou-Juey
authors.initials: KJ
authors.lastname: Wu
mesh_terms: D000818:Animals; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D045744:Cell Line, Tumor / Q000473:pathology; D002465:Cell Movement; D054338:Cell Transdifferentiation; D019008:Drug Resistance, Neoplasm; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D000072100:Jagged-1 Protein; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D000072099:Serrate-Jagged Proteins; D015398:Signal Transduction; D051879:Twist-Related Protein 1 / Q000235:genetics / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
chemical_list: D002135:Calcium-Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; C000606273:JAG1 protein, human; C000606274:Jag1 protein, mouse; D000072100:Jagged-1 Protein; C000715467:KLF4 protein, human; C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; D008565:Membrane Proteins; D009687:Nuclear Proteins; D000072099:Serrate-Jagged Proteins; C103173:TWIST1 protein, human; D051879:Twist-Related Protein 1