The epithelial–mesenchymal transition (EMT) phenomenon

Savagner, Pierre

doi:10.1093/annonc/mdq292

Cited by 344 publications

(322 citation statements)

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“…43 Thus, we did perform the evaluation of E-Cadherin, N-Cadherin and laminin expression following the treatment of RAPA and 3-MA (Figs. 4 and 5), and found that exposure to RAPA or 3-MA resulted in disorder of adhesion molecule expression in early chick embryo.…”

Section: Discussionmentioning

confidence: 99%

Autophagy functions on EMT in gastrulation of avian embryo

Wang

et al. 2014

Cell Cycle

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y These authors contributed equally to this work.Keywords: autophagy, Atg7, EMT and chick embryo, gastrulation Abbreviations: 3-MA, 3-Methyladenine; BF, bright-field; DAPI, 49-6-Diamidino-2-phenylindole; EB, embryoid bodies; E-Cad, E-cadherin; EMTs, epithelial-mesenchymal transitions; GFP, green fluorescent protein; HN, Hensen's node; MAPILC3(LC3), microtubule-associated protein 1 light chain 3; mTOR, mammalian target of rapamycin; N-Cad, N-cadherin; NT, neural tube; PBS, phosphate-buffered saline; PCD, Programmed cell death; PD, idiopathic Parkinson's Disease; PI3K, phosphoinositide-3-kinase; PPIA, peptidylprolyl isomerase A; PS, primitive streak; RAPA, Rapamycin; RT-PCR, reverse transcription PCR; shh, sonic hedgehog.Autophagy is important for cell renewing for its contribution to the degradation of bulk cytoplasm, long-lived proteins, and entire organelles and its role in embryonic development is largely unknown. In our study, we investigated the function of autophagy in gastrulation of the chick embryo using both in vivo and in vitro approaches, especially in the EMT process, and we found that autophagy gene Atg7 was expressed on the apical side of the ectoderm and endoderm. Over-expression of Atg7 could enhance the expression of Atg8 and the E-cadherin, the latter of which is a crucial marker of the EMT process. We also found that the disturbance of autophagy could retard the development of chick embryos in HH4 with shorter primitive steak than that in the control group, which is a newly formed structure during EMT process. So we assumed that autophagy could affect EMT process by adhesion molecule expression. Moreover, more molecules, such as slug, chordin, shh et., which were all involved in EMT process, were detected to address the mechanism of this phenomena. We established that the inhibition of autophagy could cause developmental delay by affecting EMT process in gastrulation of chick embryos.

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Section: Discussionmentioning

confidence: 99%

Autophagy functions on EMT in gastrulation of avian embryo

Wang

et al. 2014

Cell Cycle

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“…In the absence of ECM attachment, cells undergo a form of apoptosis known as anoikis [29] . It is thought that anoikis-resistant cells contribute to the epithelial-mesenchymal transition (EMT), which is one of the metastatic components that lead to a more flexible and migratory phenotype [30] . In an attempt to gain further insight into the biochemical features underlying the EMT, we selected anoikis-resistant cells by culturing the breast cancer cell line MDA-MB-231 on poly-HEMA-coated tissue culture plates.…”

Section: Discussionmentioning

confidence: 99%

Cross-regulation between protein L-isoaspartyl O-methyltransferase and ERK in epithelial mesenchymal transition of MDA-MB-231 cells

et al. 2011

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Aim: Protein L-isoaspartyl O-methyltransferase (PIMT) regulates cell adhesion in various cancer cell lines through activation of integrin αv and the PI3K pathway. The epithelial mesenchymal transition (EMT) enables epithelial cells to acquire the characteristics of mesenchymal cells, and to allow them to migrate for metastasis. Here, we examined the relationship between PIMT and EMT with attached or detached MDA-MB 231 cells. Methods: Human breast cancer cell line MDA-MB-231 cells were maintained in a suspension on poly-HEMA in the presence or absence of PIMT siRNA or ERK inhibitor PD98059. The mRNAs and proteins were analyzed using RT-PCR and immunoblotting, respectively. Results: During cellular incubation under detached conditions, PIMT, integrin αv and EMT proteins, such as Snail, Slug and matrix metalloproteinase 2 (MMP-2), were significantly increased in correlation with the phosphorylation of ERK1/2. The ERK inhibitor PD98059 (25 µmol/L) strongly suppressed the expression of the proteins and PIMT. Interestingly, PIMT siRNA blocked the phosphorylation of ERK and the expression of the EMT proteins. Additionally, PIMT and ERK phosphorylation were both co-activated by treatment with TGF-β (10 ng/mL) and TNF-α (10 ng/mL). Conclusion: A tight cross-regulation exists between ERK and PIMT in regards to their activation and expression during the EMT. Because the role of PIMT in the EMT and metastatic processes remains unclear, in this study, we explored the involvement of PIMT in the regulation of the detachment and attachment of the anoikis-resistant cell line MDA-MB-231, an aggressive breast cancer cell line with a highly invasive, migrative, and metastatic characters [10] , by culturing the cells in poly-HEMA (2-hydroxyethylmethacrylate)-coated dishes and introducing siRNA specific for PIMT. Materials and methods MaterialsLiCl and poly-HEMA were purchased from Sigma-Aldrich (St Louis, MO, USA). Dulbecco's modified Eagle's medium (DMEM), penicillin/streptomycin solution (10 000 unit/mL and 10 mg/mL, respectively), fetal bovine serum (FBS) and Dulbecco's phosphate-buffered saline (DPBS) were purchased from Gibco BRL (Gaithersburg, MD, USA). MDA-MB 231 cells were obtained from American Type Culture Collection (Manassas, VA, USA). Moloney murine leukemia virus (M-MLV) reverse transcriptase, polymerase chain reaction (PCR) premix, and Sapphire Super Taq were purchased from Rexgene Biotech Co, Ltd (Ochang, Korea). All primers used for PCR were purchased from Bioneer (Taejeon, Korea). A mixture of Stealth TM /siRNA duplex oligoribonucleotides against PIMT and Lipofectamine TM RNAiMAX was purchased from Invitrogen (Carlsbad, CA, USA). Rabbit anti-PIMT antiserum was produced against recombinant PIMT proteins of porcine brain as previously described (Koh and Hong, unpublished data). Antibodies against MAPK, MMP-2, MMP-9, N-cadherin, integrin αv, phospho-GSK3 (Tyr 279/216 ), phospho-ERK1/2 (Thr 202 /Tyr 204 ), phospho-MEK1 (Ser 218/222 )/MEK2 (Ser 222/226 ), phospho-Akt1/PkBα (Ser 473 ) and phospho-p90RSK (Ser 380 ) were...

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“…133 Cytoskeletal proteins are also rearranged during EMT; 134 for example, in certain epithelial cancers a characteristic increase in vimentin expression and loss of cytokeratins is observed. 135 An intermediate filament in melanoma that may be of significance in EMT is nestin, a biomarker of multilineage progenitor cells that is expressed by migrating and proliferating neural crest stem cells during embryogenesis. 136 Nestin expression is associated with cell migration and metastasis in prostate cancer, 137 and tumor progression and deceased survival in melanoma.…”

Section: How Primitive Melanoma Cells May Encourage 'Vasculogenic Mimmentioning

confidence: 99%

Melanoma stem cells: not rare, but well done

Girouard

Murphy

2011

Laboratory Investigation

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Since the identification of self-renewing cells in the hematopoietic system, stem cells have transformed the study of medicine. Cancer biologists have identified stem-like cells in multiple malignancies, including those of solid organs. This has led to the development of a stem cell theory of cancer, which purports that a subpopulation of self-renewing tumor cells is responsible for tumorigenesis. This contrasts with the stochastic model of tumor development, which advances that all tumor cells are capable of tumor formation. Within the field of melanoma, the identity and existence of cancer stem cells has been the subject of recent debate. Much of the controversy may be traced to differences in interpretations and definitions related to the cancer stem cell theory, and the use of dissimilar methodologies to study melanoma cells. Accumulating evidence suggests that cancer stem cells may exist in melanoma, although their frequency may vary and they may be capable of phenotypic plasticity. Importantly, these primitive melanoma cells are not only capable of self-renewal and differentiation plasticity, but also may confer virulence via immune evasion and multidrug resistance, and potentially via vasculogenic mimicry and transition to migratory and metastasizing derivatives. Therapeutic targeting of melanoma stem cells and the pathways that endow them with virulence hold promise for the design of more effective strategies for amelioration and eradication of this most lethal form of skin cancer.

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The epithelial–mesenchymal transition (EMT) phenomenon

Cited by 344 publications

References 36 publications

Autophagy functions on EMT in gastrulation of avian embryo

Autophagy functions on EMT in gastrulation of avian embryo

Cross-regulation between protein L-isoaspartyl O-methyltransferase and ERK in epithelial mesenchymal transition of MDA-MB-231 cells

Melanoma stem cells: not rare, but well done

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