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Identification of a ZEB2-MITF-ZEB1 transcriptional network that controls melanogenesis and melanoma progression

Geertrui Denecker (UGent) , Niels Vandamme (UGent) , Ozden Akay (UGent) , D Koludrovic, Joachim Taminau (UGent) , Kelly Lemeire (UGent) , Alexander Gheldof (UGent) , Bram De Craene (UGent) , Mireille Van Gele (UGent) , Lieve Brochez (UGent) , et al.
(2014) CELL DEATH AND DIFFERENTIATION. 21(8). p.1250-1261
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Abstract
Deregulation of signaling pathways that control differentiation, expansion and migration of neural crest-derived melanoblasts during normal development contributes also to melanoma progression and metastasis. Although several epithelial-to-mesenchymal (EMT) transcription factors, such as zinc finger E-box binding protein 1 (ZEB1) and ZEB2, have been implicated in neural crest cell biology, little is known about their role in melanocyte homeostasis and melanoma. Here we show that mice lacking Zeb2 in the melanocyte lineage exhibit a melanoblast migration defect and, unexpectedly, a severe melanocyte differentiation defect. Loss of Zeb2 in the melanocyte lineage results in a downregulation of the Microphthalmia-associated transcription factor (Mitf) and melanocyte differentiation markers concomitant with an upregulation of Zeb1. We identify a transcriptional signaling network in which the EMT transcription factor ZEB2 regulates MITF levels to control melanocyte differentiation. Moreover, our data are also relevant for human melanomagenesis as loss of ZEB2 expression is associated with reduced patient survival.
Keywords
CANCER, GENE, MOUSE, DISEASE, EXPRESSION, TUMOR PROGRESSION, MALIGNANT-MELANOMA, CUTANEOUS MELANOMA, STEM-CELL MAINTENANCE, MICE

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Chicago
Denecker, Geertrui, Niels Vandamme, Ozden Akay, D Koludrovic, Joachim Taminau, Kelly Lemeire, Alexander Gheldof, et al. 2014. “Identification of a ZEB2-MITF-ZEB1 Transcriptional Network That Controls Melanogenesis and Melanoma Progression.” Cell Death and Differentiation 21 (8): 1250–1261.
APA
Denecker, G., Vandamme, N., Akay, O., Koludrovic, D., Taminau, J., Lemeire, K., Gheldof, A., et al. (2014). Identification of a ZEB2-MITF-ZEB1 transcriptional network that controls melanogenesis and melanoma progression. CELL DEATH AND DIFFERENTIATION, 21(8), 1250–1261.
Vancouver
1.
Denecker G, Vandamme N, Akay O, Koludrovic D, Taminau J, Lemeire K, et al. Identification of a ZEB2-MITF-ZEB1 transcriptional network that controls melanogenesis and melanoma progression. CELL DEATH AND DIFFERENTIATION. 2014;21(8):1250–61.
MLA
Denecker, Geertrui, Niels Vandamme, Ozden Akay, et al. “Identification of a ZEB2-MITF-ZEB1 Transcriptional Network That Controls Melanogenesis and Melanoma Progression.” CELL DEATH AND DIFFERENTIATION 21.8 (2014): 1250–1261. Print.
@article{5670175,
  abstract     = {Deregulation of signaling pathways that control differentiation, expansion and migration of neural crest-derived melanoblasts during normal development contributes also to melanoma progression and metastasis. Although several epithelial-to-mesenchymal (EMT) transcription factors, such as zinc finger E-box binding protein 1 (ZEB1) and ZEB2, have been implicated in neural crest cell biology, little is known about their role in melanocyte homeostasis and melanoma. Here we show that mice lacking Zeb2 in the melanocyte lineage exhibit a melanoblast migration defect and, unexpectedly, a severe melanocyte differentiation defect. Loss of Zeb2 in the melanocyte lineage results in a downregulation of the Microphthalmia-associated transcription factor (Mitf) and melanocyte differentiation markers concomitant with an upregulation of Zeb1. We identify a transcriptional signaling network in which the EMT transcription factor ZEB2 regulates MITF levels to control melanocyte differentiation. Moreover, our data are also relevant for human melanomagenesis as loss of ZEB2 expression is associated with reduced patient survival.},
  author       = {Denecker, Geertrui and Vandamme, Niels and Akay, Ozden and Koludrovic, D and Taminau, Joachim and Lemeire, Kelly and Gheldof, Alexander and De Craene, Bram and Van Gele, Mireille and Brochez, Lieve and Udupi, GM and Rafferty, M and Balint, B and Gallagher, WM and Ghanem, G and Huylebroeck, D and Haigh, Jody and van den Oord, J and Larue, L and Davidson, I and Marine, JC and Berx, Geert},
  issn         = {1350-9047},
  journal      = {CELL DEATH AND DIFFERENTIATION},
  keyword      = {CANCER,GENE,MOUSE,DISEASE,EXPRESSION,TUMOR PROGRESSION,MALIGNANT-MELANOMA,CUTANEOUS MELANOMA,STEM-CELL MAINTENANCE,MICE},
  language     = {eng},
  number       = {8},
  pages        = {1250--1261},
  title        = {Identification of a ZEB2-MITF-ZEB1 transcriptional network that controls melanogenesis and melanoma progression},
  url          = {http://dx.doi.org/10.1038/cdd.2014.44},
  volume       = {21},
  year         = {2014},
}

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