Evidence for a partial epithelial–mesenchymal transition in postnatal stages of rat auditory organ morphogenesis

Johnen, Nicolas; Francart, Marie-Emilie; Thelen, Nicolas; Cloes, Marie; Thiry, Marc

doi:10.1007/s00418-012-0969-5

Cited by 24 publications

(20 citation statements)

References 34 publications

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“…Co-stained E-cadherin and Vimentin in hybrid cell lines suggested the occurrence of hybrid transcriptional program. Partial EMT has also been described during development, wound healing in addition to tumorigenesis (39–42), while the existence of subpopulation of E-cadherin-positive and vimentin-positive cells has been recently indicated in head and neck cancer (43, 44), supporting the need to further characterize this group at the genomic and proteomic levels as we have undertaken in this study. In addition, our immunohistochemical studies of CDH1 and VIM protein were performed using non-serial section of lung adenocarcinoma tissues.…”

Section: Discussionsupporting

confidence: 61%

Molecular Portraits of Epithelial, Mesenchymal, and Hybrid States in Lung Adenocarcinoma and Their Relevance to Survival

et al. 2015

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Epithelial to mesenchymal transition (EMT) is a key process associated with tumor progression and metastasis. To define molecular features associated with EMT states, we undertook an integrative approach combining mRNA, microRNA, DNA methylation and proteomic profiles of 38 cell populations representative of the genomic heterogeneity in lung adenocarcinoma were integrated with functional profiles consisting of cell invasiveness, adhesion and motility. A subset of cell lines that were readily defined as epithelial or mesenchymal based on their morphology and E-cadherin and vimentin expression elicited distinctive molecular signatures. However, most cell populations displayed intermediate/hybrid states of EMT, with mixed epithelial and mesenchymal characteristics. A dominant proteomic feature of aggressive hybrid cell lines was upregulation of cytoskeletal and actin binding proteins, a signature shared with mesenchymal cell lines. Cytoskeletal reorganization preceded loss of E-cadherin in epithelial cells in which EMT was induced by TGFβ. A set of transcripts corresponding to the mesenchymal protein signature enriched in cytoskeletal proteins was found to be predictive of survival in independent datasets of lung adenocarcinomas. Our findings point to an association between cytoskeletal and actin-binding proteins, a mesenchymal or hybrid EMT phenotype and invasive properties of lung adenocarcinomas.

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Section: Discussionsupporting

confidence: 61%

Molecular Portraits of Epithelial, Mesenchymal, and Hybrid States in Lung Adenocarcinoma and Their Relevance to Survival

et al. 2015

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“…Other markers such as N-cadherin or fibronectin either has no change or even has reduced expression, and this phenomenon has been described as partial EMT (Leroy and Mostov, 2007) and differs from classical EMT, in which all mesenchymal markers change concurrently. Partial EMT is also common for cells that do not acquire full EMT markers (Johnen et al ., 2012; Roxanis, 2013), owning the special character of Cr(VI) in cross-linking DNA, we consider this might be a cell type or promoter specific event, as A549 cells do not have the similar responses. Future works are required to explore the mechanisms of EMT in these cells.…”

Section: Discussionmentioning

confidence: 99%

Epithelial–mesenchymal transition during oncogenic transformation induced by hexavalent chromium involves reactive oxygen species-dependent mechanism in lung epithelial cells

Ding

Yao

et al. 2013

Toxicology and Applied Pharmacology

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Hexavalent Chromium [Cr(VI)] is an important human carcinogen associated with pulmonary diseases and lung cancer. Exposure to Cr(VI) induces DNA damage, cell morphological change and malignant transformation in human lung epithelial cells. Despite extensive studies, the molecular mechanisms remain elusive, it is also not known if Cr(VI)-induced transformation might accompany with invasive properties to facilitate metastasis. We aimed to study Cr(VI)-induced epithelial–mesenchymal transition (EMT) and invasion during oncogenic transformation in lung epithelial cells. The results showed that Cr(VI) at low doses represses E-cadherin mRNA and protein expression, enhances mesenchymal marker vimentin expression and transforms the epithelial cell into fibroblastoid morphology. Cr(VI) also increases cell invasion and promotes colony formation. Further studies indicated that Cr(VI) uses multiple mechanisms to repress E-cadherin expression, including activation of E-cadherin repressors such as Slug, ZEB1, KLF8 and enhanced binding of HDAC1 in E-cadherin gene promoter, but DNA methylation is not responsible for the loss of E-cadherin. Catalase reduces Cr(VI)-induced E-cadherin and vimentin protein expression, attenuates cell invasion in matrigel and colony formation on soft agar. These results demonstrate that exposure to a common human carcinogen, Cr(VI), induces EMT and invasion during oncogenic transformation in lung epithelial cells and implicate in cancer metastasis and prevention.

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“…The hybrid E/M state, also referred to as partial EMT (pEMT), can revert to the epithelial phenotype when required, as seen during the final stages of branching morphogenesis and wound healing (9)(10)(11)(12). More recently, this hybrid state has been observed at different stages of epiboly (13), organ morphogenesis (14), and metastasis (15)(16)(17).…”

Section: Introductionmentioning

confidence: 99%

Toward Decoding the Principles of Cancer Metastasis Circuits

Jolly

Onuchic

et al. 2014

Cancer Research

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Understanding epithelial-mesenchymal transitions (EMT) during cancer metastasis remains a major challenge in modern biology. Recent observations of cell behavior together with progress in mapping the underlying regulatory genetic networks led to new understandings of carcinoma metastasis. It is now established that the genetic network that regulates the EMT also enables an epithelial-mesenchymal hybrid phenotype. These hybrid cells possess mixed carcinoma epithelial and mesenchymal characteristics that enable specialized capabilities such as collective cell migration. On the gene network perspective, a fourcomponent decision unit composed of two highly interconnected chimeric modules-the miR34/SNAIL and the miR200/ZEB mutual-inhibition feedback circuits-regulates the coexistence of and transitions between the different phenotypes. Here, we present a new tractable theoretical framework to model and decode the underlying principles governing the operation of the regulatory unit. Our approach connects the knowledge about intracellular pathways with observations of cellular behavior and advances toward understanding the logic of cancer decision-making. We found that the miR34/SNAIL module acts as an integrator while the miR200/ZEB module acts as a three-way switch. Consequently, the combined unit can give rise to three phenotypes (stable states): (i) a high miR200 and low ZEB, or (1, 0) state; (ii) a low miR200 and high ZEB, or (0, 1) state; and (iii) a medium miR200 and medium ZEB, or ( 1 / 2 , 1 / 2 ) state. We associate these states with the epithelial, mesenchymal, and hybrid phenotypes, respectively. We reflect on the consistency between our theoretical predictions and recent observations in several types of carcinomas and suggest new testable predictions.

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Evidence for a partial epithelial–mesenchymal transition in postnatal stages of rat auditory organ morphogenesis

Cited by 24 publications

References 34 publications

Molecular Portraits of Epithelial, Mesenchymal, and Hybrid States in Lung Adenocarcinoma and Their Relevance to Survival

Molecular Portraits of Epithelial, Mesenchymal, and Hybrid States in Lung Adenocarcinoma and Their Relevance to Survival

Epithelial–mesenchymal transition during oncogenic transformation induced by hexavalent chromium involves reactive oxygen species-dependent mechanism in lung epithelial cells

Toward Decoding the Principles of Cancer Metastasis Circuits

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