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1.
Cancer Res ; 80(14): 2983-2995, 2020 07 15.
Article in English | MEDLINE | ID: mdl-32503808

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. SIGNIFICANCE: ZEB2 function exerts opposing behaviors in melanoma by promoting proliferation and expansion and conversely inhibiting invasiveness, which could be of future clinical relevance. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/80/14/2983/F1.large.jpg.


Subject(s)
Cell Proliferation , Epithelial-Mesenchymal Transition , Gene Expression Regulation, Neoplastic , Lung Neoplasms/secondary , Melanoma/pathology , Transcription Factors/metabolism , Zinc Finger E-box Binding Homeobox 2/metabolism , Animals , Humans , Lung Neoplasms/genetics , Lung Neoplasms/metabolism , Melanoma/genetics , Melanoma/metabolism , Mice , Neoplasm Invasiveness , Transcription Factors/genetics , Tumor Cells, Cultured , Zinc Finger E-box Binding Homeobox 2/genetics
2.
Nat Methods ; 14(3): 228-232, 2017 02 28.
Article in English | MEDLINE | ID: mdl-28245209

ABSTRACT

We argue that the field of extracellular vesicle (EV) biology needs more transparent reporting to facilitate interpretation and replication of experiments. To achieve this, we describe EV-TRACK, a crowdsourcing knowledgebase (http://evtrack.org) that centralizes EV biology and methodology with the goal of stimulating authors, reviewers, editors and funders to put experimental guidelines into practice.


Subject(s)
Biomedical Research , Databases, Bibliographic , Extracellular Vesicles/physiology , Internationality
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