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The EMT transcription factor ZEB2 promotes proliferation of primary and metastatic melanoma while suppressing an invasive, mesenchymal-like phenotype

Niels Vandamme (UGent) , Geertrui Denecker (UGent) , Kenneth Bruneel, Gillian Blancke (UGent) , Ozden Akay, Joachim Taminau (UGent) , Jordy De Coninck (UGent) , Eva De Smedt (UGent) , Nicolas Skrypek (UGent) , Wouter Van Loocke (UGent) , et al.
(2020) CANCER RESEARCH. 80(14). p.2983-2995
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Abstract
Epithelial-to-mesenchymal transition (EMT)-inducing transcription factors (TF) are well known for their ability to induce mesenchymal states associated with increased migratory and invasive properties. Unexpectedly, nuclear expression of the EMT-TF ZEB2 in human primary melanoma has been shown to correlate with reduced invasion. We report here that ZEB2 is required for outgrowth for primary melanomas and metastases at secondary sites. Ablation of Zeb2 hampered outgrowth of primary melanomas in vivo, whereas ectopic expression enhanced proliferation and growth at both primary and secondary sites. Gain of Zeb2 expression in pulmonary-residing melanoma cells promoted the development of macroscopic lesions. In vivo fate mapping made clear that melanoma cells undergo a conversion in state where ZEB2 expression is replaced by ZEB1 expression associated with gain of an invasive phenotype. These findings suggest that reversible switching of the ZEB2/ZEB1 ratio enhances melanoma metastatic dissemination.
Keywords
EXPRESSION, CELLS, GENE, RESISTANCE, NETWORK, SWITCH

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MLA
Vandamme, Niels, et al. “The EMT Transcription Factor ZEB2 Promotes Proliferation of Primary and Metastatic Melanoma While Suppressing an Invasive, Mesenchymal-like Phenotype.” CANCER RESEARCH, vol. 80, no. 14, 2020, pp. 2983–95, doi:10.1158/0008-5472.CAN-19-2373.
APA
Vandamme, N., Denecker, G., Bruneel, K., Blancke, G., Akay, O., Taminau, J., … Berx, G. (2020). The EMT transcription factor ZEB2 promotes proliferation of primary and metastatic melanoma while suppressing an invasive, mesenchymal-like phenotype. CANCER RESEARCH, 80(14), 2983–2995. https://doi.org/10.1158/0008-5472.CAN-19-2373
Chicago author-date
Vandamme, Niels, Geertrui Denecker, Kenneth Bruneel, Gillian Blancke, Ozden Akay, Joachim Taminau, Jordy De Coninck, et al. 2020. “The EMT Transcription Factor ZEB2 Promotes Proliferation of Primary and Metastatic Melanoma While Suppressing an Invasive, Mesenchymal-like Phenotype.” CANCER RESEARCH 80 (14): 2983–95. https://doi.org/10.1158/0008-5472.CAN-19-2373.
Chicago author-date (all authors)
Vandamme, Niels, Geertrui Denecker, Kenneth Bruneel, Gillian Blancke, Ozden Akay, Joachim Taminau, Jordy De Coninck, Eva De Smedt, Nicolas Skrypek, Wouter Van Loocke, Jasper Wouters, David Nittner, Corinna Kohler, Douglas S. Darling, Phil F. Cheng, Marieke I. G. Raaijmakers, Mitchell P. Levesque, Udupi Girish Mallya, Mairin Rafferty, Balazs Balint, William M. Gallagher, Lieve Brochez, Danny Huylebroeck, Jody J. Haigh, Vanessa Andries, Florian Rambow, Pieter Van Vlierberghe, Steven Goossens, Joost J. van den Oord, Jean-Christophe Marine, and Geert Berx. 2020. “The EMT Transcription Factor ZEB2 Promotes Proliferation of Primary and Metastatic Melanoma While Suppressing an Invasive, Mesenchymal-like Phenotype.” CANCER RESEARCH 80 (14): 2983–2995. doi:10.1158/0008-5472.CAN-19-2373.
Vancouver
1.
Vandamme N, Denecker G, Bruneel K, Blancke G, Akay O, Taminau J, et al. The EMT transcription factor ZEB2 promotes proliferation of primary and metastatic melanoma while suppressing an invasive, mesenchymal-like phenotype. CANCER RESEARCH. 2020;80(14):2983–95.
IEEE
[1]
N. Vandamme et al., “The EMT transcription factor ZEB2 promotes proliferation of primary and metastatic melanoma while suppressing an invasive, mesenchymal-like phenotype,” CANCER RESEARCH, vol. 80, no. 14, pp. 2983–2995, 2020.
@article{8671753,
  abstract     = {{Epithelial-to-mesenchymal transition (EMT)-inducing transcription factors (TF) are well known for their ability to induce mesenchymal states associated with increased migratory and invasive properties. Unexpectedly, nuclear expression of the EMT-TF ZEB2 in human primary melanoma has been shown to correlate with reduced invasion. We report here that ZEB2 is required for outgrowth for primary melanomas and metastases at secondary sites. Ablation of Zeb2 hampered outgrowth of primary melanomas in vivo, whereas ectopic expression enhanced proliferation and growth at both primary and secondary sites. Gain of Zeb2 expression in pulmonary-residing melanoma cells promoted the development of macroscopic lesions. In vivo fate mapping made clear that melanoma cells undergo a conversion in state where ZEB2 expression is replaced by ZEB1 expression associated with gain of an invasive phenotype. These findings suggest that reversible switching of the ZEB2/ZEB1 ratio enhances melanoma metastatic dissemination.}},
  author       = {{Vandamme, Niels and Denecker, Geertrui and Bruneel, Kenneth and Blancke, Gillian and Akay, Ozden and Taminau, Joachim and De Coninck, Jordy and De Smedt, Eva and Skrypek, Nicolas and Van Loocke, Wouter and Wouters, Jasper and Nittner, David and Kohler, Corinna and Darling, Douglas S. and Cheng, Phil F. and Raaijmakers, Marieke I. G. and Levesque, Mitchell P. and Mallya, Udupi Girish and Rafferty, Mairin and Balint, Balazs and Gallagher, William M. and Brochez, Lieve and Huylebroeck, Danny and Haigh, Jody J. and Andries, Vanessa and Rambow, Florian and Van Vlierberghe, Pieter and Goossens, Steven and van den Oord, Joost J. and Marine, Jean-Christophe and Berx, Geert}},
  issn         = {{0008-5472}},
  journal      = {{CANCER RESEARCH}},
  keywords     = {{EXPRESSION,CELLS,GENE,RESISTANCE,NETWORK,SWITCH}},
  language     = {{eng}},
  number       = {{14}},
  pages        = {{2983--2995}},
  title        = {{The EMT transcription factor ZEB2 promotes proliferation of primary and metastatic melanoma while suppressing an invasive, mesenchymal-like phenotype}},
  url          = {{http://doi.org/10.1158/0008-5472.CAN-19-2373}},
  volume       = {{80}},
  year         = {{2020}},
}
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