Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
7.8
5.6
Journals
IJMS
Special Issues
The Epithelial-to-Mesenchymal Transition (EMT) in Cancers
ijms-logo
Submit to IJMS Review for IJMS Propose a Special Issue

Journal Menu

► Journal Menu

Journal Browser

► Journal Browser
share announcement

The Epithelial-to-Mesenchymal Transition (EMT) in Cancers

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Oncology".

Deadline for manuscript submissions: closed (31 December 2021) | Viewed by 31156

Special Issue Editors

Prof. Dr. Muh-Hwa Yang

E-Mail Website
Guest Editor
Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei 112, Taiwan
Interests: epithelial-mesenchymal transition (EMT); cancer metastasis; signalling pathway; cancer progression; tumor microenvironment; cell-cell interactions; exosomes; cell migration
Dr. Isabel Fabregat

E-Mail Website1 Website2
Guest Editor
1. TGF-β and Cancer Group, Oncobell Program, Bellvitge Biomedical Research Institute (IDIBELL), Gran Via de l'Hospitalet, 199, L'Hospitalet, 08908 Barcelona, Spain
2. Oncology Program, CIBEREHD, Instituto de Salud Carlos III, 28029 Madrid, Spain
3. Department of Physiological Sciences, Faculty of Medicine and Health Sciences, University of Barcelona, L'Hospitalet, 08907 Barcelona, Spain
Interests: liver; TGF-beta; EGF; NADPH oxidases; NOX4; oxidative stress; epithelial mesenchymal transition (EMT); liver stem cells; metabolism and liver; liver cancer; HCC; liver fibrosis; liver signaling
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Epithelial-to-mesenchymal transition (EMT) is an important event in embryonic development; the transition of epithelial cells to mesenchymal cells allows the formation of adult tissues and organs. Although EMT plays an important role during embryonic development, it is also aberrantly activated during cancer metastasis. EMT allows cancer cells to acquire migratory and invasive phenotypes that lead to the dissemination of tumor cells throughout the body. In addition, cancer cells that have undergone EMT have increased resistance to apoptosis, oncogene-induced senescence, and exhibit increased resistance to chemotherapy. Almost 80% of malignant tumors are derived from the epithelial tissues of different organs such as the lung, colon, breast, pancreas, prostate, bladder, ovary, kidney, and liver. Moreover, cancer cells in early tumor states remain epithelial and have cohesive cell–cell junctions that inhibit their movements, and therefore they do not have migratory and/or invasive properties. Upon overexpression of mesenchymal specific factors, such as fibronectin, vimentin, or neural cadherin (N-cadherin), the epithelial tumor cells exhibit mesenchymal features, such as mobility and invasion.

EMT is modulated at different levels of control, such as transcriptional control, epigenetic modifications, alternative splicing, translational regulation, and microRNA-mediated gene silencing. Moreover, the cellular transdifferentiation from epithelial to mesenchymal states is regulated by many signaling pathways, of which the Ras-ERK, MAPK, and TGF-β pathways are among the best characterized. These pathways trigger the activation of key transcription factors that serve as master regulators of cell–cell adhesion, cell polarity, and motility.

However, despite the intense research over the last 20 years, our knowledge about how all these components regulate the transition is very limited. More research is necessary to understand the EMT mechanism and will help us to identify appropriate drug targets. This Special Issue will discuss the different aspects of EMT.

Prof. Dr. Muh-Hwa Yang
Dr. Isabel Fabregat
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Epithelial–mesenchymal transition
  • Hybrid epithelial/mesenchymal state
  • Tumor microenvironments
  • Tumor immunology
  • Epigenetics
  • Tumor metabolism
  • Exosomes
  • Therapy

Published Papers (8 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Research

Jump to: Review

14 pages, 2626 KiB  
Article
Particulate Matter (PM10) Promotes Cell Invasion through Epithelial–Mesenchymal Transition (EMT) by TGF-β Activation in A549 Lung Cells
by Claudia M. García-Cuellar, Miguel Santibáñez-Andrade, Yolanda I. Chirino, Raúl Quintana-Belmares, Rocío Morales-Bárcenas, Ericka Marel Quezada-Maldonado and Yesennia Sánchez-Pérez
Int. J. Mol. Sci. 2021, 22(23), 12632; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222312632 - 23 Nov 2021
Cited by 12 | Viewed by 2126
Abstract
Air pollution presents a major environmental problem, inducing harmful effects on human health. Particulate matter of 10 μm or less in diameter (PM10) is considered an important risk factor in lung carcinogenesis. Epithelial–mesenchymal transition (EMT) is a regulatory program capable of [...] Read more.
Air pollution presents a major environmental problem, inducing harmful effects on human health. Particulate matter of 10 μm or less in diameter (PM10) is considered an important risk factor in lung carcinogenesis. Epithelial–mesenchymal transition (EMT) is a regulatory program capable of inducing invasion and metastasis in cancer. In this study, we demonstrated that PM10 treatment induced phosphorylation of SMAD2/3 and upregulation of SMAD4. We also reported that PM10 increased the expression and protein levels of TGFB1 (TGF-β), as well as EMT markers SNAI1 (Snail), SNAI2 (Slug), ZEB1 (ZEB1), CDH2 (N-cadherin), ACTA2 (α-SMA), and VIM (vimentin) in the lung A549 cell line. Cell exposed to PM10 also showed a decrease in the expression of CDH1 (E-cadherin). We also demonstrated that expression levels of these EMT markers were reduced when cells are transfected with small interfering RNAs (siRNAs) against TGFB1. Interestingly, phosphorylation of SMAD2/3 and upregulation of SMAD induced by PM10 were not affected by transfection of TGFB1 siRNAs. Finally, cells treated with PM10 exhibited an increase in the capacity of invasiveness because of EMT induction. Our results provide new evidence regarding the effect of PM10 in EMT and the acquisition of an invasive phenotype, a hallmark necessary for lung cancer progression. Full article
(This article belongs to the Special Issue The Epithelial-to-Mesenchymal Transition (EMT) in Cancers)
►▼ Show Figures

Figure 1

10 pages, 1571 KiB  
Article
Cisplatin Plus Cetuximab Inhibits Cisplatin-Resistant Human Oral Squamous Cell Carcinoma Cell Migration and Proliferation but Does Not Enhance Apoptosis
by Hyeong Sim Choi, Young-Kyun Kim and Pil-Young Yun
Int. J. Mol. Sci. 2021, 22(15), 8167; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22158167 - 29 Jul 2021
Cited by 8 | Viewed by 2091
Abstract
Cisplatin is among the most widely used anticancer drugs used in the treatment of several malignancies, including oral cancer. However, cisplatin treatment often promotes chemical resistance, subsequently causing treatment failure. Several studies have shown that epidermal growth factor receptors (EGFRs) play a variety [...] Read more.
Cisplatin is among the most widely used anticancer drugs used in the treatment of several malignancies, including oral cancer. However, cisplatin treatment often promotes chemical resistance, subsequently causing treatment failure. Several studies have shown that epidermal growth factor receptors (EGFRs) play a variety of roles in cancer progression and overcoming cisplatin resistance. Therefore, this study focused on EGFR inhibitors used in novel targeted therapies as a method to overcome this resistance. We herein aimed to determine whether the combined effects of cisplatin and cetuximab could enhance cisplatin sensitivity by inhibiting the epithelial-to-mesenchymal transition (EMT) process in cisplatin-resistant cells. In vitro analyses of three cisplatin-resistant oral squamous cell carcinoma cells, which included cell proliferation assay, combination index calculation, cell cytotoxicity assay, live/dead cell count assay, Western blot assay, propidium iodide staining assay, scratch assay, and qRT-PCR assay were then conducted. Our results showed that a cisplatin/cetuximab combination treatment inhibited cell proliferation, cell motility, and N-cadherin protein expression but induced E-cadherin and claudin-1 protein expression. Although the combination of cisplatin and cetuximab did not induce apoptosis of cisplatin-resistant cells, it may be useful in treating oral cancer patients with cisplatin resistance given that it controls cell motility and EMT-related proteins. Full article
(This article belongs to the Special Issue The Epithelial-to-Mesenchymal Transition (EMT) in Cancers)
►▼ Show Figures

Figure 1

15 pages, 5241 KiB  
Article
Epithelial–Mesenchymal Transition (EMT) Induced by TGF-β in Hepatocellular Carcinoma Cells Reprograms Lipid Metabolism
by Jitka Soukupova, Andrea Malfettone, Esther Bertran, María Isabel Hernández-Alvarez, Irene Peñuelas-Haro, Francesco Dituri, Gianluigi Giannelli, Antonio Zorzano and Isabel Fabregat
Int. J. Mol. Sci. 2021, 22(11), 5543; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22115543 - 24 May 2021
Cited by 33 | Viewed by 4127
Abstract
(1) Background: The transforming growth factor (TGF)-β plays a dual role in liver carcinogenesis. At early stages, it inhibits cell growth and induces apoptosis. However, TGF-β expression is high in advanced stages of hepatocellular carcinoma (HCC) and cells become resistant to TGF-β induced [...] Read more.
(1) Background: The transforming growth factor (TGF)-β plays a dual role in liver carcinogenesis. At early stages, it inhibits cell growth and induces apoptosis. However, TGF-β expression is high in advanced stages of hepatocellular carcinoma (HCC) and cells become resistant to TGF-β induced suppressor effects, responding to this cytokine undergoing epithelial–mesenchymal transition (EMT), which contributes to cell migration and invasion. Metabolic reprogramming has been established as a key hallmark of cancer. However, to consider metabolism as a therapeutic target in HCC, it is necessary to obtain a better understanding of how reprogramming occurs, which are the factors that regulate it, and how to identify the situation in a patient. Accordingly, in this work we aimed to analyze whether a process of full EMT induced by TGF-β in HCC cells induces metabolic reprogramming. (2) Methods: In vitro analysis in HCC cell lines, metabolomics and transcriptomics. (3) Results: Our findings indicate a differential metabolic switch in response to TGF-β when the HCC cells undergo a full EMT, which would favor lipolysis, increased transport and utilization of free fatty acids (FFA), decreased aerobic glycolysis and an increase in mitochondrial oxidative metabolism. (4) Conclusions: EMT induced by TGF-β in HCC cells reprograms lipid metabolism to facilitate the utilization of FFA and the entry of acetyl-CoA into the TCA cycle, to sustain the elevated requirements of energy linked to this process. Full article
(This article belongs to the Special Issue The Epithelial-to-Mesenchymal Transition (EMT) in Cancers)
►▼ Show Figures

Figure 1

Review

Jump to: Research

13 pages, 1564 KiB  
Review
The Epithelial-to-Mesenchymal Transition (EMT) in the Development and Metastasis of Malignant Pleural Mesothelioma
by Valeria Ramundo, Giada Zanirato and Elisabetta Aldieri
Int. J. Mol. Sci. 2021, 22(22), 12216; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222212216 - 11 Nov 2021
Cited by 22 | Viewed by 3125
Abstract
Malignant pleural mesothelioma (MPM) is an aggressive tumor mainly associated with asbestos exposure and is characterized by a very difficult pharmacological approach. One of the molecular mechanisms associated with cancer onset and invasiveness is the epithelial-to-mesenchymal transition (EMT), an event induced by different [...] Read more.
Malignant pleural mesothelioma (MPM) is an aggressive tumor mainly associated with asbestos exposure and is characterized by a very difficult pharmacological approach. One of the molecular mechanisms associated with cancer onset and invasiveness is the epithelial-to-mesenchymal transition (EMT), an event induced by different types of inducers, such as transforming growth factor β (TGFβ), the main inducer of EMT, and oxidative stress. MPM development and metastasis have been correlated to EMT; On one hand, EMT mediates the effects exerted by asbestos fibers in the mesothelium, particularly via increased oxidative stress and TGFβ levels evoked by asbestos exposure, thus promoting a malignant phenotype, and on the other hand, MPM acquires invasiveness via the EMT event, as shown by an upregulation of mesenchymal markers or, although indirectly, some miRNAs or non-coding RNAs, all demonstrated to be involved in cancer onset and metastasis. This review aims to better describe how EMT is involved in driving the development and invasiveness of MPM, in an attempt to open new scenarios that are useful in the identification of predictive markers and to improve the pharmacological approach against this aggressive cancer. Full article
(This article belongs to the Special Issue The Epithelial-to-Mesenchymal Transition (EMT) in Cancers)
►▼ Show Figures

Graphical abstract

17 pages, 1063 KiB  
Review
Mesothelial-to-Mesenchymal Transition and Exosomes in Peritoneal Metastasis of Ovarian Cancer
by Lucía Pascual-Antón, Beatriz Cardeñes, Ricardo Sainz de la Cuesta, Lucía González-Cortijo, Manuel López-Cabrera, Carlos Cabañas and Pilar Sandoval
Int. J. Mol. Sci. 2021, 22(21), 11496; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222111496 - 25 Oct 2021
Cited by 29 | Viewed by 4028
Abstract
Most patients with ovarian cancer (OvCA) present peritoneal disseminated disease at the time of diagnosis. During peritoneal metastasis, cancer cells detach from the primary tumor and disseminate through the intraperitoneal fluid. The peritoneal mesothelial cell (PMC) monolayer that lines the abdominal cavity is [...] Read more.
Most patients with ovarian cancer (OvCA) present peritoneal disseminated disease at the time of diagnosis. During peritoneal metastasis, cancer cells detach from the primary tumor and disseminate through the intraperitoneal fluid. The peritoneal mesothelial cell (PMC) monolayer that lines the abdominal cavity is the first barrier encountered by OvCA cells. Subsequent progression of tumors through the peritoneum leads to the accumulation into the peritoneal stroma of a sizeable population of carcinoma-associated fibroblasts (CAFs), which is mainly originated from a mesothelial-to-mesenchymal transition (MMT) process. A common characteristic of OvCA patients is the intraperitoneal accumulation of ascitic fluid, which is composed of cytokines, chemokines, growth factors, miRNAs, and proteins contained in exosomes, as well as tumor and mesothelial suspended cells, among other components that vary in proportion between patients. Exosomes are small extracellular vesicles that have been shown to mediate peritoneal metastasis by educating a pre-metastatic niche, promoting the accumulation of CAFs via MMT, and inducing tumor growth and chemoresistance. This review summarizes and discusses the pivotal role of exosomes and MMT as mediators of OvCA peritoneal colonization and as emerging diagnostic and therapeutic targets. Full article
(This article belongs to the Special Issue The Epithelial-to-Mesenchymal Transition (EMT) in Cancers)
►▼ Show Figures

Figure 1

26 pages, 3119 KiB  
Review
Interplay of Immunometabolism and Epithelial–Mesenchymal Transition in the Tumor Microenvironment
by Ming-Yu Chou and Muh-Hwa Yang
Int. J. Mol. Sci. 2021, 22(18), 9878; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22189878 - 13 Sep 2021
Cited by 13 | Viewed by 3532
Abstract
Epithelial–mesenchymal transition (EMT) and metabolic reprogramming in cancer cells are the key hallmarks of tumor metastasis. Since the relationship between the two has been well studied, researchers have gained increasing interest in the interplay of cancer cell EMT and immune metabolic changes. Whether [...] Read more.
Epithelial–mesenchymal transition (EMT) and metabolic reprogramming in cancer cells are the key hallmarks of tumor metastasis. Since the relationship between the two has been well studied, researchers have gained increasing interest in the interplay of cancer cell EMT and immune metabolic changes. Whether the mutual influences between them could provide novel explanations for immune surveillance during metastasis is worth understanding. Here, we review the role of immunometabolism in the regulatory loop between tumor-infiltrating immune cells and EMT. We also discuss the challenges and perspectives of targeting immunometabolism in cancer treatment. Full article
(This article belongs to the Special Issue The Epithelial-to-Mesenchymal Transition (EMT) in Cancers)
►▼ Show Figures

Figure 1

21 pages, 841 KiB  
Review
The Role of the IL-6 Cytokine Family in Epithelial–Mesenchymal Plasticity in Cancer Progression
by Andrea Abaurrea, Angela M. Araujo and Maria M. Caffarel
Int. J. Mol. Sci. 2021, 22(15), 8334; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22158334 - 03 Aug 2021
Cited by 43 | Viewed by 5404
Abstract
Epithelial–mesenchymal plasticity (EMP) plays critical roles during embryonic development, wound repair, fibrosis, inflammation and cancer. During cancer progression, EMP results in heterogeneous and dynamic populations of cells with mixed epithelial and mesenchymal characteristics, which are required for local invasion and metastatic dissemination. Cancer [...] Read more.
Epithelial–mesenchymal plasticity (EMP) plays critical roles during embryonic development, wound repair, fibrosis, inflammation and cancer. During cancer progression, EMP results in heterogeneous and dynamic populations of cells with mixed epithelial and mesenchymal characteristics, which are required for local invasion and metastatic dissemination. Cancer development is associated with an inflammatory microenvironment characterized by the accumulation of multiple immune cells and pro-inflammatory mediators, such as cytokines and chemokines. Cytokines from the interleukin 6 (IL-6) family play fundamental roles in mediating tumour-promoting inflammation within the tumour microenvironment, and have been associated with chronic inflammation, autoimmunity, infectious diseases and cancer, where some members often act as diagnostic or prognostic biomarkers. All IL-6 family members signal through the Janus kinase (JAK)–signal transducer and activator of transcription (STAT) pathway and are able to activate a wide array of signalling pathways and transcription factors. In general, IL-6 cytokines activate EMP processes, fostering the acquisition of mesenchymal features in cancer cells. However, this effect may be highly context dependent. This review will summarise all the relevant literature related to all members of the IL-6 family and EMP, although it is mainly focused on IL-6 and oncostatin M (OSM), the family members that have been more extensively studied. Full article
(This article belongs to the Special Issue The Epithelial-to-Mesenchymal Transition (EMT) in Cancers)
►▼ Show Figures

Figure 1

23 pages, 1828 KiB  
Review
The Post-Translational Regulation of Epithelial–Mesenchymal Transition-Inducing Transcription Factors in Cancer Metastasis
by Eunjeong Kang, Jihye Seo, Haelim Yoon and Sayeon Cho
Int. J. Mol. Sci. 2021, 22(7), 3591; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22073591 - 30 Mar 2021
Cited by 43 | Viewed by 5357
Abstract
Epithelial–mesenchymal transition (EMT) is generally observed in normal embryogenesis and wound healing. However, this process can occur in cancer cells and lead to metastasis. The contribution of EMT in both development and pathology has been studied widely. This transition requires the up- and [...] Read more.
Epithelial–mesenchymal transition (EMT) is generally observed in normal embryogenesis and wound healing. However, this process can occur in cancer cells and lead to metastasis. The contribution of EMT in both development and pathology has been studied widely. This transition requires the up- and down-regulation of specific proteins, both of which are regulated by EMT-inducing transcription factors (EMT-TFs), mainly represented by the families of Snail, Twist, and ZEB proteins. This review highlights the roles of key EMT-TFs and their post-translational regulation in cancer metastasis. Full article
(This article belongs to the Special Issue The Epithelial-to-Mesenchymal Transition (EMT) in Cancers)
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-8
Back to TopTop