Epithelial-mesenchymal transition: focus on metastatic cascade, alternative splicing, non-coding RNAs and modulating compounds

Samatov, Timur R.; Tonevitsky, Alexander G.; Schumacher, Udo

doi:10.1186/1476-4598-12-107

Cited by 127 publications

(96 citation statements)

References 96 publications

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“…In addition, as displayed above, EMT is highly regulated by a large number of signaling pathways. These pathways are targetable by drugs currently tested in preclinical studies or clinical trials in CCA, such as the EGFR inhibitor erlotinib (see reviews [13,148]). …”

Section: Targeting Emt Pathwaysmentioning

confidence: 99%

Epithelial-mesenchymal transition in cholangiocarcinoma: From clinical evidence to regulatory networks

Vaquero

Guedj

Clapéron

et al. 2017

Journal of Hepatology

113

122

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Cholangiocarcinoma (CCA) is an aggressive tumor with a poor prognosis due to its late clinical presentation and the lack of effective non-surgical therapies. Unfortunately, most of the patients are not eligible for curative surgery owing to the presence of metastases at the time of diagnosis. Therefore, it is important to understand the steps leading to cell dissemination in patients with CCA. To metastasize from the primary site, cancer cells must acquire migratory and invasive properties by a cell plasticity-promoting phenomenon known as epithelial-mesenchymal transition (EMT). EMT is a reversible dynamic process by which epithelial cells gradually adopt structural and functional characteristics of mesenchymal cells, and has lately become a center of attention in the field of metastatic dissemination. In the present review, we aim to provide an extensive overview of the current clinical data and the prognostic value of different EMT markers that have been analyzed in CCA. We summarize all the regulatory networks implicated in EMT from the membrane receptors to the main EMT-inducing transcription factors (SNAIL, TWIST and ZEB). Furthermore, since a tumor is a complex structure not exclusively formed by tumor cells, we also address the prominent role of the main cell types of the desmoplastic stroma that characterizes CCA in the regulation of EMT. Finally, we discuss the therapeutic considerations and difficulties faced to develop an effective anti-EMT treatment due to the redundancies and bypasses among the pathways regulating EMT. 4Key Point Box -EMT is an early event of metastasis that endows tumor cells with invasive properties enabling them to spread toward other territories.-EMT contributes to CCA progression and chemoresistance.-The three families of transcription factors that regulate epithelial and mesenchymal marker expression during EMT (SNAIL, TWIST and ZEB) contribute to CCA progression.-Cells of CCA microenvironment, and not only cancer cells, lead to the activation of EMT.

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Section: Targeting Emt Pathwaysmentioning

confidence: 99%

Epithelial-mesenchymal transition in cholangiocarcinoma: From clinical evidence to regulatory networks

Vaquero

Guedj

Clapéron

et al. 2017

Journal of Hepatology

113

122

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“…Although there are many theories for tumor metastasis, such as seed and soil hypothesis [16][17][18], and epithelial-to-mesenchymal transition (EMT) [19,20], full details of the underlying mechanism remain to be elucidated. At present, miRNAs research provides a new direction for tumor metastasis.…”

Section: Discussionmentioning

confidence: 99%

“…In brief, total RNAs were extracted by using Trizol in accordance with the manufacturer's instructions. Reverse transcriptase reactions contained RNA samples, 50 nM stem-loop RT primer (Table 1), 19 RT buffer (Biosystems), 0.25 mM each of dNTPs, 3.33 U/mL MultiScribe reverse transcriptase (Biosystems), and 0.25 U/mL RNase inhibitor (Applied Biosystems). The 7.5 lL reactions were incubated in a ABI 7900 cycler for 30 min at 16°C, 30 min at 42°C, 5 min at 85°C, and then held at a constant temperature of 4°C.…”

Section: Real-time Polymerase Chain Reaction (Real-time Pcr)mentioning

confidence: 99%

Anti-miR-362-3p Inhibits Migration and Invasion of Human Gastric Cancer Cells by Its Target CD82

Yao

et al. 2015

Dig Dis Sci

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“…Metastasis is based on a complex, multi-step process called the metastatic cascade [1]. In carcinomas, i.e.…”

Section: Introductionmentioning

confidence: 99%

Ion channels and transporters in metastasis

Stock

Schwab

2015

Biochimica et Biophysica Acta (BBA) - Biomembranes

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An elaborate interplay between ion channels and transporters, components of the cytoskeleton, adhesion molecules, and signaling cascades provides the basis for each major step of the metastatic cascade. Ion channels and transporters contribute to cell motility by letting through or transporting ions essential for local Ca2+, pH and--in cooperation with water permeable aquaporins--volume homeostasis. Moreover, in addition to the actual ion transport they, or their auxiliary subunits, can display non-conducting activities. They can exert kinase activity in order to phosphorylate cytoskeletal constituents or their associates. They can become part of signaling processes by permeating Ca2+, by generating local pH-nanodomains or by being final downstream effectors. A number of channels and transporters are found at focal adhesions, interacting directly or indirectly with proteins of the extracellular matrix, with integrins or with components of the cytoskeleton. We also include the role of aquaporins in cell motility. They drive the outgrowth of lamellipodia/invadopodia or control the number of β1 integrins in the plasma membrane. The multitude of interacting ion channels and transporters (called transportome) including the associated signaling events holds great potential as therapeutic target(s) for anticancer agents that are aimed at preventing metastasis. This article is part of a Special Issue entitled: Membrane channels and transporters in cancers.

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Epithelial-mesenchymal transition: focus on metastatic cascade, alternative splicing, non-coding RNAs and modulating compounds

Cited by 127 publications

References 96 publications

Epithelial-mesenchymal transition in cholangiocarcinoma: From clinical evidence to regulatory networks

Epithelial-mesenchymal transition in cholangiocarcinoma: From clinical evidence to regulatory networks

Anti-miR-362-3p Inhibits Migration and Invasion of Human Gastric Cancer Cells by Its Target CD82

Ion channels and transporters in metastasis

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