Transitions between epithelial and mesenchymal states in development and disease

Baum, Buzz; Settleman, Jeffrey; Quinlan, Margaret P.

doi:10.1016/j.semcdb.2008.02.001

Cited by 351 publications

(246 citation statements)

References 175 publications

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“…EMT is a normal physiological process that is essential for embryogenesis and tissue morphogenesis and for tissue remodeling and repair during wound healing. 4,[29][30] However, pathological EMT is increasingly recognized to have an important role during the development of human diseases, including chronic inflammation, fibrosis, rheumatoid arthritis and cancer invasion and metastasis. 3,[31][32] miRNAs are endogenous small non-coding RNAs that control the target gene expression at the post-transcriptional level.…”

Section: Discussionmentioning

confidence: 99%

Critical role of miR-10b in transforming growth factor-β1-induced epithelial–mesenchymal transition in breast cancer

et al. 2014

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Epithelial-mesenchymal transition (EMT) is a key process in the tumor metastatic cascade that is characterized by the loss of cell-cell junctions and cell polarity, resulting in the acquisition of migratory and invasive properties. Recent evidence showed that altered microRNA-10b (miR-10b) expression was implicated in the occurrence of EMT of breast cancer. However, the exact role and underlying mechanisms of miR-10b in the EMT of breast cancer still remain unknown. In this study, miR-10b was found to be upregulated in breast cancer tissues and breast cancer cell lines and the expression of miR-10b was shown to be closely correlated with aggressiveness in breast cancer. Treating breast cancer cells with the miR-10b inhibitor increased E-cadherin expression while decreasing vimentin expression. At the same time, on inhibition of miR-10b, the invasion and proliferation ability of breast cancer cells also decreased. Transforming growth factor-b (TGF-b) is a multifunctional cytokine that induces EMT in multiple cell types. Here, we identified miR-10b as a target gene of TGF-b1. The expression of miR-10b increased during TGF-b1-induced EMT of breast cancer cells. Further study showed that inhibition of miR-10b expression partially reversed the EMT, invasion and proliferation induced by TGF-b1 in breast cancer cells. Taken together, these results demonstrated a novel function for miR-10b in TGF-b1-induced EMT in breast cancer and increased their metastatic potential. MiR-10b might become a possible target for gene therapy in breast cancer.Cancer Gene Therapy (2014) 21, 60-67; doi:10.1038/cgt.2013.82; published online 24 January 2014Keywords: miR-10b; TGF-b1; EMT; E-cadherin; invasion Breast cancer is one of the most common types of malignant cancers worldwide. Even though there has been considerable progress in the early detection and surgical therapy of breast cancer, there are B350 000 women who die from breast cancer each year. 1 The principal reason for mortality in breast cancer is invasion and metastasis rather than the primary cancer itself; therefore, there is an urgent need to understand the molecular mechanism and pathways that participate in the invasion and metastasis of breast cancer for better and improved treatment of women diagnosed with breast cancer. 2 Epithelial-mesenchymal transition (EMT) is a key step toward cancer metastasis, and E-cadherin is regarded as a main indicator of the epithelial-mesenchymal phenotype switching. 3 E-cadherin loss is suggestive of EMT, and tumor cell invasion and metastasis are associated with EMT. [4][5] EMT is triggered by many signaling pathways-for example, transforming growth factor-b (TGF-b), 6 fibroblast growth factor, 7 epidermal growth factor, 8 hepatocyte growth factor, 9 plateletderived growth factors 10 as well as different isoforms of Wnt proteins, 11 matrix metalloproteinases, 12 bone morphogenic proteins 13 and many others. Among these signaling pathways, TGF-b has been claimed to be critical for induction of the EMT phenotype, and TGF-b as a potent induc...

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Section: Discussionmentioning

confidence: 99%

Critical role of miR-10b in transforming growth factor-β1-induced epithelial–mesenchymal transition in breast cancer

et al. 2014

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“…Epithelial cells are connected by E-cadherin-based adherens junctions which have to be dissolved as part of a process called epithelial-to-mesenchymal transition (EMT) to allow migration. EMT is on one hand a physiological process involved in many developmental processes as well as wound healing, but on the other hand it is also intimately linked to metastasis initiation [96]. As E-cadherin is the main component of epithelial adherens junctions, its removal is crucial for the dissolution of epithelial cell cell contacts.…”

Section: Trafficking Of Other Cell Surface Adhesions Proteinsmentioning

confidence: 99%

On the move: endocytic trafficking in cell migration

Maritzen

Schachtner

Legler

2015

Cell. Mol. Life Sci.

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Directed cell migration is a fundamental process underlying diverse physiological and pathophysiological phenomena ranging from wound healing and induction of immune responses to cancer metastasis. Recent advances reveal that endocytic trafficking contributes to cell migration in multiple ways. (1) At the level of chemokines and chemokine receptors: internalization of chemokines by scavenger receptors is essential for shaping chemotactic gradients in tissue, whereas endocytosis of chemokine receptors and their subsequent recycling is key for maintaining a high responsiveness of migrating cells. (2) At the level of integrin trafficking and focal adhesion dynamics: endosomal pathways do not only modulate adhesion by delivering integrins to their site of action, but also by supplying factors for focal adhesion disassembly. (3) At the level of extracellular matrix reorganization: endosomal transport contributes to tumor cell migration not only by targeting integrins to invadosomes but also by delivering membrane type 1 matrix metalloprotease to the leading edge facilitating proteolysis-dependent chemotaxis. Consequently, numerous endocytic and endosomal factors have been shown to modulate cell migration. In fact key modulators of endocytic trafficking turn out to be also key regulators of cell migration. This review will highlight the recent progress in unraveling the contribution of cellular trafficking pathways to cell migration.

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“…Indeed, mounting evidence suggests that co‐opting of EMT, an evolutionarily conserved process required for tissue morphogenesis during embryonic development, plays a critical role in tumor invasion, acquisition of cancer stem cell‐like properties, and the development of metastasis and drug resistance 4. While loss of E‐cadherin expression represents a primal event in EMT, we increasingly appreciate that EMT is a complex process that is orchestrated by activation and repression of a growing and still incomplete list of genes, proteins, and transcriptional factors including ZEB1, SNAIL, TWIST, CDH2, and VIM among others 5, 6, 7.…”

Section: Introductionmentioning

confidence: 99%

Transcriptome profiling reveals novel gene expression signatures and regulating transcription factors of TGFβ‐induced epithelial‐to‐mesenchymal transition

Yamamoto

Burnette

et al. 2016

Cancer Medicine

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Dysregulated epithelial to mesenchymal transition (EMT) in cancer cells endows invasive and metastatic properties upon cancer cells that favor successful colonization of distal target organs and therefore play a critical role in transforming early‐stage carcinomas into invasive malignancies. EMT has also been associated with tumor recurrence and drug resistance and cancer stem cell initiation. Therefore, better understanding of the mechanisms behind EMT could ultimately contribute to the development of novel prognostic approaches and individualized therapies that specifically target EMT processes. As an effort to characterize the central transcriptome changes during EMT, we have developed a Transforming growth factor (TGF)‐beta‐based in vitro EMT model and used it to profile EMT‐related gene transcriptional changes in two different cell lines, a non‐small cell lung cancer cell line H358, and a breast cell line MCF10a. After 7 days of TGF‐beta/Oncostatin M (OSM) treatment, changes in cell morphology to a mesenchymal phenotype were observed as well as concordant EMT‐associated changes in mRNA and protein expression. Further, increased motility was noted and flow cytometry confirmed enrichment in cancer stem cell‐like populations. Microarray‐based differential expression analysis identified an EMT‐associated gene expression signature which was confirmed by RT‐qPCR and which significantly overlapped with a previously published EMT core signature. Finally, two novel EMT‐regulating transcription factors, IRF5 and LMCD1, were identified and independently validated.

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Transitions between epithelial and mesenchymal states in development and disease

Cited by 351 publications

References 175 publications

Critical role of miR-10b in transforming growth factor-β1-induced epithelial–mesenchymal transition in breast cancer

Critical role of miR-10b in transforming growth factor-β1-induced epithelial–mesenchymal transition in breast cancer

On the move: endocytic trafficking in cell migration

Transcriptome profiling reveals novel gene expression signatures and regulating transcription factors of TGFβ‐induced epithelial‐to‐mesenchymal transition

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