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Biomedicines
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Epithelial-to-Mesenchymal Transition (EMT) in Cancer
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Epithelial-to-Mesenchymal Transition (EMT) in Cancer

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Cancer Biology and Oncology".

Deadline for manuscript submissions: closed (30 June 2021) | Viewed by 13775

Special Issue Editor

Dr. Amit Bera

E-Mail Website
Guest Editor
Atlantic Cancer Research Institute, Moncton, NB E1C 8X3, Canada
Interests: cap-independent translation regulations; EMT; microRNA; eIF3e; ITAFs; heterogeneous ribonucleoproteins; diabetic nephropathy; cell signalling

Special Issue Information

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, including 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 trans-differentiation 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 for last twenty years, our knowledge is very limited about how all these components regulate the transition. More research is necessary to understand the EMT mechanism and it will help us to identify appropriate drug target. This special issue will discuss the different aspect of EMT.

Dr. Amit Bera
Guest Editor

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. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). 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

  • EMT
  • migration
  • invasion
  • metastasis
  • cancer progression

Published Papers (4 papers)

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Research

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18 pages, 2306 KiB  
Article
Exploring Epithelial–Mesenchymal Transition Signals in Endometriosis Diagnosis and In Vitro Fertilization Outcomes
by Vito Cela, Elisa Malacarne, Maria Elena Rosa Obino, Ilaria Marzi, Francesca Papini, Francesca Vergine, Elena Pisacreta, Elisa Zappelli, Deborah Pietrobono, Giorgia Scarfò, Simona Daniele, Ferdinando Franzoni, Claudia Martini and Paolo Giovanni Artini
Biomedicines 2021, 9(11), 1681; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines9111681 - 12 Nov 2021
Cited by 11 | Viewed by 2108
Abstract
Endometriosis (EMS) pathogenesis has been related to the release of inflammatory mediators in peritoneal fluid, creating an altered microenvironment that leads to low-grade oocyte/embryos and to the reduction of implantation rates. The Epithelial–Mesenchymal Transition (EMT), an inflammation-related process, can be a further contributing [...] Read more.
Endometriosis (EMS) pathogenesis has been related to the release of inflammatory mediators in peritoneal fluid, creating an altered microenvironment that leads to low-grade oocyte/embryos and to the reduction of implantation rates. The Epithelial–Mesenchymal Transition (EMT), an inflammation-related process, can be a further contributing factor to EMS. This study aimed to investigate, among various cytokines and EMT markers (Cadherins, TGF-β, HIF-1α), diagnostic markers of EMS and prognostic factors of in vitro fertilization (IVF) outcomes. Herein, EMS patients manifested higher serum levels of the inflammatory molecules IL-6, IL-8, and IL-12 and a decrease in the concentrations of the anti-inflammatory IL-10. Moreover, biochemical markers associated with the EMT process were more elevated in serum and follicular fluid (FF) of EMS patients than in controls. At the end, the number of good-quality embryos was inversely related to serum IL-6 and EMT markers. Interestingly, serum IL-6 and FF IL-10 concentrations differentiated EMS patients from controls. Finally, serum IL-8 and E-Cadherin levels, as well as FF IL-10, predicted positive IVF outcome with great accuracy. Our data confirm the pivotal role of inflammatory mediators (i.e., IL-6 and IL-10) in EMS pathogenesis and suggest that EMT-related markers are elevated in EMS patients and can be predictive of IVF outcome. Full article
(This article belongs to the Special Issue Epithelial-to-Mesenchymal Transition (EMT) in Cancer)
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Review

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28 pages, 6289 KiB  
Review
Stationed or Relocating: The Seesawing EMT/MET Determinants from Embryonic Development to Cancer Metastasis
by Chien-Hsiu Li, Tai-I Hsu, Yu-Chan Chang, Ming-Hsien Chan, Pei-Jung Lu and Michael Hsiao
Biomedicines 2021, 9(9), 1265; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines9091265 - 18 Sep 2021
Cited by 11 | Viewed by 3917
Abstract
Epithelial and mesenchymal transition mechanisms continue to occur during the cell cycle and throughout human development from the embryo stage to death. In embryo development, epithelial-mesenchymal transition (EMT) can be divided into three essential steps. First, endoderm, mesoderm, and neural crest cells form, [...] Read more.
Epithelial and mesenchymal transition mechanisms continue to occur during the cell cycle and throughout human development from the embryo stage to death. In embryo development, epithelial-mesenchymal transition (EMT) can be divided into three essential steps. First, endoderm, mesoderm, and neural crest cells form, then the cells are subdivided, and finally, cardiac valve formation occurs. After the embryonic period, the human body will be subjected to ongoing mechanical stress or injury. The formation of a wound requires EMT to recruit fibroblasts to generate granulation tissues, repair the wound and re-create an intact skin barrier. However, once cells transform into a malignant tumor, the tumor cells acquire the characteristic of immortality. Local cell growth with no growth inhibition creates a solid tumor. If the tumor cannot obtain enough nutrition in situ, the tumor cells will undergo EMT and invade the basal membrane of nearby blood vessels. The tumor cells are transported through the bloodstream to secondary sites and then begin to form colonies and undergo reverse EMT, the so-called “mesenchymal-epithelial transition (MET).” This dynamic change involves cell morphology, environmental conditions, and external stimuli. Therefore, in this manuscript, the similarities and differences between EMT and MET will be dissected from embryonic development to the stage of cancer metastasis. Full article
(This article belongs to the Special Issue Epithelial-to-Mesenchymal Transition (EMT) in Cancer)
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18 pages, 596 KiB  
Review
Exploring Hyperoxia Effects in Cancer—From Perioperative Clinical Data to Potential Molecular Mechanisms
by Anca Irina Ristescu, Crina Elena Tiron, Adrian Tiron and Ioana Grigoras
Biomedicines 2021, 9(9), 1213; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines9091213 - 13 Sep 2021
Cited by 4 | Viewed by 2116
Abstract
Increased inspiratory oxygen concentration is constantly used during the perioperative period of cancer patients to prevent the potential development of hypoxemia and to provide an adequate oxygen transport to the organs, tissues and cells. Although the primary tumours are surgically removed, the effects [...] Read more.
Increased inspiratory oxygen concentration is constantly used during the perioperative period of cancer patients to prevent the potential development of hypoxemia and to provide an adequate oxygen transport to the organs, tissues and cells. Although the primary tumours are surgically removed, the effects of perioperative hyperoxia exposure on distal micro-metastases and on circulating cancer cells can potentially play a role in cancer progression or recurrence. In clinical trials, hyperoxia seems to increase the rate of postoperative complications and, by delaying postoperative recovery, it can alter the return to intended oncological treatment. The effects of supplemental oxygen on the long-term mortality of surgical cancer patients offer, at this point, conflicting results. In experimental studies, hyperoxia effects on cancer biology were explored following multiple pathways. In cancer cell cultures and animal models, hyperoxia increases the production of reactive oxygen species (ROS) and increases the oxidative stress. These can be followed by the induction of the expression of Brain-derived neurotrophic factor (BDNF) and other molecules involved in angiogenesis and by the promotion of various degrees of epithelial mesenchymal transition (EMT). Full article
(This article belongs to the Special Issue Epithelial-to-Mesenchymal Transition (EMT) in Cancer)
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14 pages, 1670 KiB  
Review
Role of Calcium Homeostasis in Modulating EMT in Cancer
by Clark A. Jones and Lori A. Hazlehurst
Biomedicines 2021, 9(9), 1200; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines9091200 - 11 Sep 2021
Cited by 15 | Viewed by 4716
Abstract
Calcium is essential for cells to perform numerous physiological processes. In cancer, the augmentation of calcium signaling supports the more proliferative and migratory cells, which is a characteristic of the epithelial-to-mesenchymal transition (EMT). By genetically and epigenetically modifying genes, channels, and entire signaling [...] Read more.
Calcium is essential for cells to perform numerous physiological processes. In cancer, the augmentation of calcium signaling supports the more proliferative and migratory cells, which is a characteristic of the epithelial-to-mesenchymal transition (EMT). By genetically and epigenetically modifying genes, channels, and entire signaling pathways, cancer cells have adapted to survive with an extreme imbalance of calcium that allows them to grow and metastasize in an abnormal manner. This cellular remodeling also allows for the evasion of immune surveillance and the development of drug resistance, which lead to poor prognosis in patients. Understanding the role calcium flux plays in driving the phenotypes associated with invasion, immune suppression, metastasis, and drug resistance remains critical for determining treatments to optimize clinical outcomes and future drug discovery. Full article
(This article belongs to the Special Issue Epithelial-to-Mesenchymal Transition (EMT) in Cancer)
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