ijms-logo

Journal Browser

Journal Browser

Special Issue "Epithelial-Mesenchymal Transition (EMT) 2021"

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

Deadline for manuscript submissions: closed (30 November 2021) | Viewed by 8370

Special Issue Editors

Prof. Dr. Monica Fedele
E-Mail Website
Guest Editor
Prof. Dr. Manfioletti Guidalberto
E-Mail Website
Guest Editor
Department of Life Sciences, University of Trieste, 34127 Trieste, Italy
Interests: high mobility group A (HMGA) proteins; chromatin; regulation of gene expression; protein–protein interactions; post-translational modifications (PTMs); epithelial–mesenchymal transition; proteomics; tumor microenvironment; breast cancer; metastasis
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The epithelial–mesenchymal transition (EMT), a biological process that allows an epithelial cell to assume a mesenchymal phenotype, including enhanced migratory capacity, invasiveness, elevated resistance to apoptosis, stem-like features, and increased production of ECM components, occurs during specific steps of embryogenesis and organ development leading to final differentiation. Due to its plasticity and reversibility, terminally differentiated epithelium can transdifferentiate and change its phenotype through EMT. This process can also be activated in a pathological situation, such as tissue injury and repair or neoplastic transformation. Indeed, it is now well recognized that EMT constitutes the first step for the invasiveness and metastatic dissemination of epithelial cancer cells. Moreover, acquisition of mesenchymal features in non-epithelial cancers, such as glioblastomas, has been associated with invasiveness and aggressiveness of the tumor, together with a worse prognosis of the patients.

The EMT program is initiated by different molecular processes, including activation of transcriptional factors, expression of specific cell-surface proteins, reorganization and expression of cytoskeletal proteins, production of ECM-degrading enzymes, and changes in the expression of microRNAs. There are both endogenous cell autonomous and exogenous noncell autonomous signals occurring in the process, including pathways orchestrated by TGF-b, Notch, Wnt, Hedgehog, and receptor tyrosine kinases, as well as the urokinase plasminogen activator system, the secretome of associated fibroblasts, macrophages, cancer stem cells and cancer cells, and exosomes with their cargo of microRNAs.

However, despite intense investigation in recent years, relatively little is known about how all these components are integrated and participate in the same process, and how the mesenchymal state is maintained. Deep knowledge of these aspects will help to design potential therapeutic approaches that could exploit the plasticity of this process to reverse the metastatic phenotype of many cancers. Papers related to any aspect of EMT will be considered for this Special Issue.

Prof. Dr. Monica Fedele
Prof. Dr. Manfioletti Guidalberto
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

  • EMT
  • Cancer progression
  • Embryogenesis
  • Tissue injury
  • Cell motility
  • Invasion
  • Metastasis
  • Stemness

Published Papers (7 papers)

Order results
Result details
Select all
Export citation of selected articles as:

Editorial

Jump to: Research, Review

Editorial
Epithelial–Mesenchymal Transition (EMT) 2021
Int. J. Mol. Sci. 2022, 23(10), 5848; https://doi.org/10.3390/ijms23105848 - 23 May 2022
Cited by 2 | Viewed by 602
Abstract
Epithelial–mesenchymal transition (EMT) is a transdifferentiation process wherein epithelial cells acquire characteristics typical of mesenchymal cells [...] Full article
(This article belongs to the Special Issue Epithelial-Mesenchymal Transition (EMT) 2021)

Research

Jump to: Editorial, Review

Article
SYNCRIP Modulates the Epithelial-Mesenchymal Transition in Hepatocytes and HCC Cells
Int. J. Mol. Sci. 2022, 23(2), 913; https://doi.org/10.3390/ijms23020913 - 14 Jan 2022
Cited by 2 | Viewed by 751
Abstract
Heterogeneous nuclear ribonucleoproteins (hnRNPs) control gene expression by acting at multiple levels and are often deregulated in epithelial tumors; however, their roles in the fine regulation of cellular reprogramming, specifically in epithelial–mesenchymal transition (EMT), remain largely unknown. Here, we focused on the hnRNP-Q [...] Read more.
Heterogeneous nuclear ribonucleoproteins (hnRNPs) control gene expression by acting at multiple levels and are often deregulated in epithelial tumors; however, their roles in the fine regulation of cellular reprogramming, specifically in epithelial–mesenchymal transition (EMT), remain largely unknown. Here, we focused on the hnRNP-Q (also known as SYNCRIP), showing by molecular analysis that in hepatocytes it acts as a “mesenchymal” gene, being induced by TGFβ and modulating the EMT. SYNCRIP silencing limits the induction of the mesenchymal program and maintains the epithelial phenotype. Notably, in HCC invasive cells, SYNCRIP knockdown induces a mesenchymal–epithelial transition (MET), negatively regulating their mesenchymal phenotype and significantly impairing their migratory capacity. In exploring possible molecular mechanisms underlying these observations, we identified a set of miRNAs (i.e., miR-181-a1-3p, miR-181-b1-3p, miR-122-5p, miR-200a-5p, and miR-let7g-5p), previously shown to exert pro- or anti-EMT activities, significantly impacted by SYNCRIP interference during EMT/MET dynamics and gathered insights, suggesting the possible involvement of this RNA binding protein in their transcriptional regulation. Full article
(This article belongs to the Special Issue Epithelial-Mesenchymal Transition (EMT) 2021)
Show Figures

Figure 1

Article
Investigation of the Epithelial to Mesenchymal Transition (EMT) Process in Equine Papillomavirus-2 (EcPV-2)-Positive Penile Squamous Cell Carcinomas
Int. J. Mol. Sci. 2021, 22(19), 10588; https://doi.org/10.3390/ijms221910588 - 30 Sep 2021
Cited by 3 | Viewed by 807
Abstract
Equine penile squamous cell carcinoma (epSCC) is the most frequent tumor of the external male genitalia, representing 67.5% of equine genital cancers. epSCC is associated with papilloma virus (PV) infection and has been recently proposed as a model for human PV-induced squamous cell [...] Read more.
Equine penile squamous cell carcinoma (epSCC) is the most frequent tumor of the external male genitalia, representing 67.5% of equine genital cancers. epSCC is associated with papilloma virus (PV) infection and has been recently proposed as a model for human PV-induced squamous cell carcinomas. It has already been suggested that epSCC might undergo epithelial-to-mesenchymal transition (EMT). This work aims to investigate in detail this process and the possible role of PV oncoproteins in epSCC. For this purpose, 18 penile SCCs were retrospectively selected and tested for both EcPV2 presence and oncoproteins (EcPV2 E6 and EcPV2 E7) expression. Moreover, immunohistochemical EMT characterization was carried out by analyzing the main epithelial markers (E-cadherin, β-catenin, and pan-cytokeratin AE3/AE1), the main mesenchymal markers (N-cadherin and vimentin), and the main EMT-related transcription factors (TWIST-1, ZEB-1). PCR analysis was positive for EcPV2 in 16 out of 18 samples. EMT was investigated in epSCC positive for EcPV2. The immunohistochemistry results suggested the presence of EMT processes in the neoplastic cells at the tumor invasive front. Moreover, the significant upregulation of RANKL, together with BCATN1, LEF1, and FOSL1 genes, might suggest a canonical Wnt pathway activation, similarly to what is reported in human penile squamous cell carcinomas Full article
(This article belongs to the Special Issue Epithelial-Mesenchymal Transition (EMT) 2021)
Show Figures

Figure 1

Communication
Expression of the E5 Oncoprotein of HPV16 Impacts on the Molecular Profiles of EMT-Related and Differentiation Genes in Ectocervical Low-Grade Lesions
Int. J. Mol. Sci. 2021, 22(12), 6534; https://doi.org/10.3390/ijms22126534 - 18 Jun 2021
Cited by 4 | Viewed by 778
Abstract
Infection with human papillomavirus type 16 (HPV16) is one of the major risk factors for the development of cervical cancer. Our previous studies have demonstrated the involvement of the early oncoprotein E5 of HPV16 (16E5) in the altered isoform switch of fibroblast growth [...] Read more.
Infection with human papillomavirus type 16 (HPV16) is one of the major risk factors for the development of cervical cancer. Our previous studies have demonstrated the involvement of the early oncoprotein E5 of HPV16 (16E5) in the altered isoform switch of fibroblast growth factor receptor 2 (FGFR2) and the consequent expression in human keratinocytes of the mesenchymal FGFR2c isoform, whose aberrant signaling leads to EMT, invasiveness, and dysregulated differentiation. Here, we aimed to establish the possible direct link between these pathological features or the appearance of FGFR2c and the expression of 16E5 in low-grade squamous intraepithelial lesions (LSILs). Molecular analysis showed that the FGFR2c expression displayed a statistically significant positive correlation with that of the viral oncoprotein, whereas the expression values of the epithelial FGR2b variant, as well as those of the differentiation markers keratin 10 (K10), loricrin (LOR) and involucrin (INV), were inversely linked to the 16E5 expression. In contrast, the expression of EMT-related transcription factors Snail1 and ZEB1 overlapped with that of 16E5, becoming a statistically significant positive correlation in the case of Snail2. Parallel analysis performed in human cervical LSIL-derived W12 cells, containing episomal HPV16, revealed that the depletion of 16E5 by siRNA was able to counteract these molecular events, proving to represent an effective strategy to identify the specific role of this viral oncoprotein in determining LSIL oncogenic and more aggressive profiles. Overall, coupling in vitro approaches to the molecular transcript analysis in ectocervical early lesions could significantly contribute to the characterization of specific gene expression profiles prognostic for those LSILs with a greater probability of direct neoplastic progression. Full article
(This article belongs to the Special Issue Epithelial-Mesenchymal Transition (EMT) 2021)
Show Figures

Figure 1

Article
BMAL1 Knockdown Leans Epithelial–Mesenchymal Balance toward Epithelial Properties and Decreases the Chemoresistance of Colon Carcinoma Cells
Int. J. Mol. Sci. 2021, 22(10), 5247; https://doi.org/10.3390/ijms22105247 - 16 May 2021
Cited by 7 | Viewed by 1187
Abstract
The circadian clock coordinates biological and physiological functions to day/night cycles. The perturbation of the circadian clock increases cancer risk and affects cancer progression. Here, we studied how BMAL1 knockdown (BMAL1-KD) by shRNA affects the epithelial–mesenchymal transition (EMT), a critical early event in [...] Read more.
The circadian clock coordinates biological and physiological functions to day/night cycles. The perturbation of the circadian clock increases cancer risk and affects cancer progression. Here, we studied how BMAL1 knockdown (BMAL1-KD) by shRNA affects the epithelial–mesenchymal transition (EMT), a critical early event in the invasion and metastasis of colorectal carcinoma (CRC). In corresponding to a gene set enrichment analysis, which showed a significant enrichment of EMT and invasive signatures in BMAL1_high CRC patients as compared to BMAL1_low CRC patients, our results revealed that BMAL1 is implicated in keeping the epithelial–mesenchymal equilibrium of CRC cells and influences their capacity of adhesion, migration, invasion, and chemoresistance. Firstly, BMAL1-KD increased the expression of epithelial markers (E-cadherin, CK-20, and EpCAM) but decreased the expression of Twist and mesenchymal markers (N-cadherin and vimentin) in CRC cell lines. Finally, the molecular alterations after BMAL1-KD promoted mesenchymal-to-epithelial transition-like changes mostly appeared in two primary CRC cell lines (i.e., HCT116 and SW480) compared to the metastatic cell line SW620. As a consequence, migration/invasion and drug resistance capacities decreased in HCT116 and SW480 BMAL1-KD cells. Together, BMAL1-KD alerts the delicate equilibrium between epithelial and mesenchymal properties of CRC cell lines, which revealed the crucial role of BMAL1 in EMT-related CRC metastasis and chemoresistance. Full article
(This article belongs to the Special Issue Epithelial-Mesenchymal Transition (EMT) 2021)
Show Figures

Figure 1

Article
Suppression of PGC-1α Drives Metabolic Dysfunction in TGFβ2-Induced EMT of Retinal Pigment Epithelial Cells
Int. J. Mol. Sci. 2021, 22(9), 4701; https://doi.org/10.3390/ijms22094701 - 29 Apr 2021
Cited by 7 | Viewed by 1523
Abstract
PGC-1α, a key orchestrator of mitochondrial metabolism, plays a crucial role in governing the energetically demanding needs of retinal pigment epithelial cells (RPE). We previously showed that silencing PGC-1α induced RPE to undergo an epithelial-mesenchymal-transition (EMT). Here, we show that induction of EMT [...] Read more.
PGC-1α, a key orchestrator of mitochondrial metabolism, plays a crucial role in governing the energetically demanding needs of retinal pigment epithelial cells (RPE). We previously showed that silencing PGC-1α induced RPE to undergo an epithelial-mesenchymal-transition (EMT). Here, we show that induction of EMT in RPE using transforming growth factor-beta 2 (TGFβ2) suppressed PGC-1α expression. Correspondingly, TGFβ2 induced defects in mitochondrial network integrity with increased sphericity and fragmentation. TGFβ2 reduced expression of genes regulating mitochondrial dynamics, reduced citrate synthase activity and intracellular ATP content. High-resolution respirometry showed that TGFβ2 reduced mitochondrial OXPHOS levels consistent with reduced expression of NDUFB5. The reduced mitochondrial respiration was associated with a compensatory increase in glycolytic reserve, glucose uptake and gene expression of glycolytic enzymes (PFKFB3, PKM2, LDHA). Treatment with ZLN005, a selective small molecule activator of PGC-1α, blocked TGFβ2-induced upregulation of mesenchymal genes (αSMA, Snai1, CTGF, COL1A1) and TGFβ2-induced migration using the scratch wound assay. Our data show that EMT is accompanied by mitochondrial dysfunction and a metabolic shift towards reduced OXPHOS and increased glycolysis that may be driven by PGC-1α suppression. ZLN005 effectively blocks EMT in RPE and thus serves as a novel therapeutic avenue for treatment of subretinal fibrosis. Full article
(This article belongs to the Special Issue Epithelial-Mesenchymal Transition (EMT) 2021)
Show Figures

Graphical abstract

Review

Jump to: Editorial, Research

Review
The Epithelial–Mesenchymal Transition at the Crossroads between Metabolism and Tumor Progression
Int. J. Mol. Sci. 2022, 23(2), 800; https://doi.org/10.3390/ijms23020800 - 12 Jan 2022
Cited by 10 | Viewed by 1406
Abstract
The transition between epithelial and mesenchymal phenotype is emerging as a key determinant of tumor cell invasion and metastasis. It is a plastic process in which epithelial cells first acquire the ability to invade the extracellular matrix and migrate into the bloodstream via [...] Read more.
The transition between epithelial and mesenchymal phenotype is emerging as a key determinant of tumor cell invasion and metastasis. It is a plastic process in which epithelial cells first acquire the ability to invade the extracellular matrix and migrate into the bloodstream via transdifferentiation into mesenchymal cells, a phenomenon known as epithelial–mesenchymal transition (EMT), and then reacquire the epithelial phenotype, the reverse process called mesenchymal–epithelial transition (MET), to colonize a new organ. During all metastatic stages, metabolic changes, which give cancer cells the ability to adapt to increased energy demand and to withstand a hostile new environment, are also important determinants of successful cancer progression. In this review, we describe the complex interaction between EMT and metabolism during tumor progression. First, we outline the main connections between the two processes, with particular emphasis on the role of cancer stem cells and LncRNAs. Then, we focus on some specific cancers, such as breast, lung, and thyroid cancer. Full article
(This article belongs to the Special Issue Epithelial-Mesenchymal Transition (EMT) 2021)
Show Figures

Figure 1

Back to TopTop