Mechanisms of the Epithelial–Mesenchymal Transition by TGF-β

Wendt, Michael K.; Allington, Tressa M.; Schiemann, William P.

doi:10.2217/fon.09.90

Cited by 287 publications

(286 citation statements)

References 238 publications

Supporting

Mentioning

273

Contrasting

Unclassified

Order By: Relevance

“…Taken together with our previous report of involvement of ATP-P2X7 signaling in TGF-β1-induced cell migration of A549 cells [17], it is possible that involvement of autocrine signaling mediated by release of ATP and activation of P2X7 receptor is a distinctive feature of cancer cell migration. Induction of migration of epithelial cells by TGF-β1 is essential for physiological processes such as wound healing [4]. We speculate that blockade of P2X7 receptor might suppress cancer cell migration without affecting physiological migration of normal epithelial cells, although further work will be needed to confirm this idea.…”

Section: Discussionmentioning

confidence: 92%

“…For example, transforming growth factor-β1 (TGF-β1) is secreted by many kinds of cancer cells and has been implicated in cancer progression, including angiogenesis, immuneescape, and metastasis [1][2][3]. TGF-β1 promotes cell migration by inducing a phenotype change called epithelialmesenchymal transition (EMT) [4]. During EMT, immotile epithelial cells differentiate into highly motile, fibroblast-like cells.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Autocrine signaling via release of ATP and activation of P2X7 receptor influences motile activity of human lung cancer cells

Takai

Tsukimoto

Hishida

et al. 2014

Purinergic Signalling

View full text Add to dashboard Cite

Extracellular nucleotides, such as ATP, are released from cells and play roles in various physiological and pathological processes through activation of P2 receptors. Here, we show that autocrine signaling through release of ATP and activation of P2X7 receptor influences migration of human lung cancer cells. Release of ATP was induced by stimulation with TGF-β1, which is a potent inducer of cell migration, in human lung cancer H292 cells, but not in noncancerous BEAS-2B cells. Treatment of H292 cells with a specific antagonist of P2X7 receptor resulted in suppression of TGF-β1-induced migration. PC-9 human lung cancer cells released a large amount of ATP under standard cell culture conditions, and P2X7 receptor-dependent dye uptake was observed even in the absence of exogenous ligand, suggesting constitutive activation of P2X7 receptor in this cell line. PC-9 cells showed high motile activity, which was inhibited by treatment with ecto-nucleotidase and P2X7 receptor antagonists, whereas a P2X7 receptor agonist enhanced migration. PC-9 cells also harbor a constitutively active mutation in epidermal growth factor receptor (EGFR). Treatment with EGFR tyrosine kinase inhibitor AG1478 suppressed both cell migration and P2X7 receptor expression in PC-9 cells. Compared to control PC-9 cells, cells treated with P2X7 antagonist exhibited broadened lamellipodia around the cell periphery, while AG1478-treated cells lacked lamellipodia. These results indicate that P2X7-mediated signaling and EGFR signaling may regulate migration of PC-9 cells through distinct mechanisms. We propose that autocrine ATP-P2X7 signaling is involved in migration of human lung cancer cells through regulation of actin cytoskeleton rearrangement.

show abstract

Section: Discussionmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Autocrine signaling via release of ATP and activation of P2X7 receptor influences motile activity of human lung cancer cells

Takai

Tsukimoto

Hishida

et al. 2014

Purinergic Signalling

View full text Add to dashboard Cite

show abstract

“…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%

“…During the intervening years since this important discovery, the findings of numerous studies have coalesced in establishing TGF-b as a master regulator of the initiation and resolution of EMT under a variety of pathophysiological contexts. 29,37 In order to examine whether miR-10b is involved in the TGF-b signaling pathway in EMT, we checked the miR-10b expression in MDA-MB-231 and MDA-MB-435 cells treated with TGF-b1 after 24 h and their corresponding parental cells. We found that, when stimulated with TGF-b1 for 24 h, MDA-MB-231 and MDA-MB-435 cells showed higher expression of miR10b.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2014

View full text Add to dashboard Cite

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...

show abstract

“…As mentioned above, carcinoma cells traversing the EMT program lose their epithelial cell polarity and cellcell adhesions and acquire mesenchymal traits, such as the ability to invade and metastasize (1). While the transcriptomic and phenotypic changes associated with these events have been extensively documented, an emerging area of EMT research focuses on the extrinsic signals that drive the reprogramming of the epigenome.…”

Section: Epigenetic Modulation Of Emt: Chromatin States Prime Cscs Fomentioning

confidence: 99%

The propensity for epithelial-mesenchymal transitions is dictated by chromatin states in the cancer cell of origin

Belle

Schiemann

2017

Stem Cell Investig.

View full text Add to dashboard Cite

Mechanisms of the Epithelial–Mesenchymal Transition by TGF-β

Cited by 287 publications

References 238 publications

Autocrine signaling via release of ATP and activation of P2X7 receptor influences motile activity of human lung cancer cells

Autocrine signaling via release of ATP and activation of P2X7 receptor influences motile activity of human lung cancer cells

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

The propensity for epithelial-mesenchymal transitions is dictated by chromatin states in the cancer cell of origin

Contact Info

Product

Resources

About