scholarly journals The Epithelial–Mesenchymal Transition at the Crossroads between Metabolism and Tumor Progression

2022 ◽  
Vol 23 (2) ◽  
pp. 800
Author(s):  
Monica Fedele ◽  
Riccardo Sgarra ◽  
Sabrina Battista ◽  
Laura Cerchia ◽  
Guidalberto Manfioletti
Keyword(s):  
Tumor Progression ◽  
Cancer Progression ◽  
Energy Demand ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Phenotype ◽  
Mesenchymal Transition ◽  
Epithelial Phenotype ◽  
Plastic Process ◽  
Mesenchymal Epithelial Transition

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.

scholarly journals Communication Between Epithelial–Mesenchymal Plasticity and Cancer Stem Cells: New Insights Into Cancer Progression

2021 ◽  
Vol 11 ◽  
Author(s):  
Xiaobo Zheng ◽  
Fuzhen Dai ◽  
Lei Feng ◽  
Hong Zou ◽  
Li Feng ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Progression ◽  
Cancer Biology ◽  
Epithelial Mesenchymal Transition ◽  
Current Knowledge ◽  
Mesenchymal Transition ◽  
Binary Model ◽  
Epithelial Phenotype

The epithelial–mesenchymal transition (EMT) is closely associated with the acquisition of aggressive traits by carcinoma cells and is considered responsible for metastasis, relapse, and chemoresistance. Molecular links between the EMT and cancer stem cells (CSCs) have indicated that EMT processes play important roles in the expression of CSC-like properties. It is generally thought that EMT-related transcription factors (EMT-TFs) need to be downregulated to confer an epithelial phenotype to mesenchymal cells and increase cell proliferation, thereby promoting metastasis formation. However, the genetic and epigenetic mechanisms that regulate EMT and CSC activation are contradictory. Emerging evidence suggests that EMT need not be a binary model and instead a hybrid epithelial/mesenchymal state. This dynamic process correlates with epithelial–mesenchymal plasticity, which indicates a contradictory role of EMT during cancer progression. Recent studies have linked the epithelial–mesenchymal plasticity and stem cell-like traits, providing new insights into the conflicting relationship between EMT and CSCs. In this review, we examine the current knowledge about the interplay between epithelial–mesenchymal plasticity and CSCs in cancer biology and evaluate the controversies and future perspectives. Understanding the biology of epithelial–mesenchymal plasticity and CSCs and their implications in therapeutic treatment may provide new opportunities for targeted intervention.

scholarly journals Grainyhead-like 2 inhibits the coactivator p300, suppressing tubulogenesis and the epithelial–mesenchymal transition

2016 ◽  
Vol 27 (15) ◽  
pp. 2479-2492 ◽  
Author(s):  
Phillip M. Pifer ◽  
Joshua C. Farris ◽  
Alyssa L. Thomas ◽  
Peter Stoilov ◽  
James Denvir ◽  
...  
Keyword(s):  
Tumor Progression ◽  
Epithelial Mesenchymal Transition ◽  
Matrix Metalloproteases ◽  
Anoikis Resistance ◽  
Mesenchymal Transition ◽  
Amino Acid Region ◽  
Epithelial Phenotype ◽  
Junctional Complexes ◽  
Coactivator P300

Developmental morphogenesis and tumor progression require a transient or stable breakdown of epithelial junctional complexes to permit programmed migration, invasion, and anoikis resistance, characteristics endowed by the epithelial–mesenchymal transition (EMT). The epithelial master-regulatory transcription factor Grainyhead-like 2 (GRHL2) suppresses and reverses EMT, causing a mesenchymal–epithelial transition to the default epithelial phenotype. Here we investigated the role of GRHL2 in tubulogenesis of Madin–Darby canine kidney cells, a process requiring transient, partial EMT. GRHL2 was required for cystogenesis, but it suppressed tubulogenesis in response to hepatocyte growth factor. Surprisingly, GRHL2 suppressed this process by inhibiting the histone acetyltransferase coactivator p300, preventing the induction of matrix metalloproteases and other p300-dependent genes required for tubulogenesis. A 13–amino acid region of GRHL2 was necessary for inhibition of p300, suppression of tubulogenesis, and interference with EMT. The results demonstrate that p300 is required for partial or complete EMT occurring in tubulogenesis or tumor progression and that GRHL2 suppresses EMT in both contexts through inhibition of p300.

scholarly journals Cell Plasticity and Prostate Cancer: The Role of Epithelial–Mesenchymal Transition in Tumor Progression, Invasion, Metastasis and Cancer Therapy Resistance

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2795
Author(s):  
Sofia Papanikolaou ◽  
Aikaterini Vourda ◽  
Spyros Syggelos ◽  
Kostis Gyftopoulos
Keyword(s):  
Prostate Cancer ◽  
Cancer Therapy ◽  
Tumor Progression ◽  
Epithelial Mesenchymal Transition ◽  
Metastatic Tumor ◽  
Therapy Resistance ◽  
Cellular Process ◽  
Cell Plasticity ◽  
Mesenchymal Transition

Prostate cancer, the second most common malignancy in men, is characterized by high heterogeneity that poses several therapeutic challenges. Epithelial–mesenchymal transition (EMT) is a dynamic, reversible cellular process which is essential in normal embryonic morphogenesis and wound healing. However, the cellular changes that are induced by EMT suggest that it may also play a central role in tumor progression, invasion, metastasis, and resistance to current therapeutic options. These changes include enhanced motility and loss of cell–cell adhesion that form a more aggressive cellular phenotype. Moreover, the reverse process (MET) is a necessary element of the metastatic tumor process. It is highly probable that this cell plasticity reflects a hybrid state between epithelial and mesenchymal status. In this review, we describe the underlying key mechanisms of the EMT-induced phenotype modulation that contribute to prostate tumor aggressiveness and cancer therapy resistance, in an effort to provide a framework of this complex cellular process.

scholarly journals LOX-1 and cancer: an indissoluble liaison

2021 ◽  
Author(s):  
M. Murdocca ◽  
C. De Masi ◽  
S. Pucci ◽  
R. Mango ◽  
G. Novelli ◽  
...  
Keyword(s):  
Tumor Progression ◽  
Epithelial Mesenchymal Transition ◽  
Vascular Endothelial Cells ◽  
Transition Process ◽  
Receptor Protein ◽  
Pancreatic Tumors ◽  
Tumor Evolution ◽  
Mesenchymal Transition ◽  
Angiogenic Proteins

AbstractRecently, a strong correlation between metabolic disorders, tumor onset, and progression has been demonstrated, directing new therapeutic strategies on metabolic targets. OLR1 gene encodes the LOX-1 receptor protein, responsible for the recognition, binding, and internalization of ox-LDL. In the past, several studied, aimed to clarify the role of LOX-1 receptor in atherosclerosis, shed light on its role in the stimulation of the expression of adhesion molecules, pro-inflammatory signaling pathways, and pro-angiogenic proteins, including NF-kB and VEGF, in vascular endothelial cells and macrophages. In recent years, LOX-1 upregulation in different tumors evidenced its involvement in cancer onset, progression and metastasis. In this review, we outline the role of LOX-1 in tumor spreading and metastasis, evidencing its function in VEGF induction, HIF-1alpha activation, and MMP-9/MMP-2 expression, pushing up the neoangiogenic and the epithelial–mesenchymal transition process in glioblastoma, osteosarcoma prostate, colon, breast, lung, and pancreatic tumors. Moreover, our studies contributed to evidence its role in interacting with WNT/APC/β-catenin axis, highlighting new pathways in sporadic colon cancer onset. The application of volatilome analysis in high expressing LOX-1 tumor-bearing mice correlates with the tumor evolution, suggesting a closed link between LOX-1 upregulation and metabolic changes in individual volatile compounds and thus providing a viable method for a simple, non-invasive alternative monitoring of tumor progression. These findings underline the role of LOX-1 as regulator of tumor progression, migration, invasion, metastasis formation, and tumor-related neo-angiogenesis, proposing this receptor as a promising therapeutic target and thus enhancing current antineoplastic strategies.

scholarly journals MBP-1 Suppresses Growth and Metastasis of Gastric Cancer Cells through COX-2

2009 ◽  
Vol 20 (24) ◽  
pp. 5127-5137 ◽  
Author(s):  
Kai-Wen Hsu ◽  
Rong-Hong Hsieh ◽  
Chew-Wun Wu ◽  
Chin-Wen Chi ◽  
Yan-Hwa Wu Lee ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Tumor Progression ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Epithelial Mesenchymal Transition ◽  
Suppressive Effect ◽  
Migration And Invasion ◽  
Gastric Cancer Cells ◽  
Mesenchymal Transition ◽  
Cox 2

The c-Myc promoter binding protein 1 (MBP-1) is a transcriptional suppressor of c-myc expression and involved in control of tumorigenesis. Gastric cancer is one of the most frequent neoplasms and lethal malignancies worldwide. So far, the regulatory mechanism of its aggressiveness has not been clearly characterized. Here we studied roles of MBP-1 in gastric cancer progression. We found that cell proliferation was inhibited by MBP-1 overexpression in human stomach adenocarcinoma SC-M1 cells. Colony formation, migration, and invasion abilities of SC-M1 cells were suppressed by MBP-1 overexpression but promoted by MBP-1 knockdown. Furthermore, the xenografted tumor growth of SC-M1 cells was suppressed by MBP-1 overexpression. Metastasis in lungs of mice was inhibited by MBP-1 after tail vein injection with SC-M1 cells. MBP-1 also suppressed epithelial-mesenchymal transition in SC-M1 cells. Additionally, MBP-1 bound on cyclooxygenase 2 (COX-2) promoter and downregulated COX-2 expression. The MBP-1-suppressed tumor progression in SC-M1 cells were through inhibition of COX-2 expression. MBP-1 also exerted a suppressive effect on tumor progression of other gastric cancer cells such as AGS and NUGC-3 cells. Taken together, these results suggest that MBP-1–suppressed COX-2 expression plays an important role in the inhibition of growth and progression of gastric cancer.

Role of Herbal Medicine/Phyto-Therapy in Cancer Prevention by Inhibiting Epithelial-Mesenchymal Transition (EMT) Pathways

2021 ◽  
pp. 215-234
Author(s):  
Rekha Gahtori ◽  
Ashutosh Paliwal
Keyword(s):  
Cancer Progression ◽  
Epithelial Mesenchymal Transition ◽  
Raw Materials ◽  
Human Life ◽  
Developed Countries ◽  
Mesenchymal Transition ◽  
Synthetic Drugs ◽  
Extracellular Signals ◽  
Different Levels

Human life is surrounded and dependent on its environment. Human civilization is nurtured by nature as it provides raw materials that are used in the manufacturing of various essential products like medicine, food items, etc. Not only developing countries but developed countries also depend on herbal-based medications. Cancer is a global health burden. Epithelial-mesenchymal-transition (EMT) plays a key role in cancer progression and is also stimulated by different extracellular signals and could be regulated at different levels. Conventional therapies exhibit a cytotoxic effect, which encourages the development of a new approach that could be used with synthetic drugs. Phytotherapy emerged as an effective weapon against cancer. Herbal drugs directly target different signaling pathways that promote EMT and eventually lead to cancer.

scholarly journals New Actors Driving the Epithelial–Mesenchymal Transition in Cancer: The Role of Leptin

Biomolecules ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 1676
Author(s):  
Monserrat Olea-Flores ◽  
Juan C. Juárez-Cruz ◽  
Miriam D. Zuñiga-Eulogio ◽  
Erika Acosta ◽  
Eduardo García-Rodríguez ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Tumor Progression ◽  
Epithelial Mesenchymal Transition ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Epithelial Cancers ◽  
Patients With Cancer

Leptin is a hormone secreted mainly by adipocytes; physiologically, it participates in the control of appetite and energy expenditure. However, it has also been linked to tumor progression in different epithelial cancers. In this review, we describe the effect of leptin on epithelial–mesenchymal transition (EMT) markers in different study models, including in vitro, in vivo, and patient studies and in various types of cancer, including breast, prostate, lung, and ovarian cancer. The different studies report that leptin promotes the expression of mesenchymal markers and a decrease in epithelial markers, in addition to promoting EMT-related processes such as cell migration and invasion and poor prognosis in patients with cancer. Finally, we report that leptin has the greatest biological relevance in EMT and tumor progression in breast, lung, prostate, esophageal, and ovarian cancer. This relationship could be due to the key role played by the enriched tumor microenvironment in adipose tissue. Together, these findings demonstrate that leptin is a key biomolecule that drives EMT and metastasis in cancer.

scholarly journals Epithelial–mesenchymal transition: role in cancer progression and the perspectives of antitumor treatment

Acta Naturae ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 4-23
Author(s):  
A. V. Gaponova ◽  
S. Rodin ◽  
A. A. Mazina ◽  
P. V. Volchkov
Keyword(s):  
Epithelial Cells ◽  
Tumor Progression ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Epithelial Mesenchymal Transition ◽  
Malignant Tumors ◽  
The Body ◽  
Epithelial Tissue ◽  
Mesenchymal Transition ◽  
Tumor Dissemination

About 90% of all malignant tumors are of epithelial nature. The epithelial tissue is characterized by a close interconnection between cells through cellcell interactions, as well as a tight connection with the basement membrane, which is responsible for cell polarity. These interactions strictly determine the location of epithelial cells within the body and are seemingly in conflict with the metastatic potential that many cancers possess (the main criteria for highly malignant tumors). Tumor dissemination into vital organs is one of the primary causes of death in patients with cancer. Tumor dissemination is based on the so-called epithelialmesenchymal transition (EMT), a process when epithelial cells are transformed into mesenchymal cells possessing high mobility and migration potential. More and more studies elucidating the role of the EMT in metastasis and other aspects of tumor progression are published each year, thus forming a promising field of cancer research. In this review, we examine the most recent data on the intracellular and extracellular molecular mechanisms that activate EMT and the role they play in various aspects of tumor progression, such as metastasis, apoptotic resistance, and immune evasion, aspects that have usually been attributed exclusively to cancer stem cells (CSCs). In conclusion, we provide a detailed review of the approved and promising drugs for cancer therapy that target the components of the EMT signaling pathways.

scholarly journals Transcription Factors in Cancer Development and Therapy

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2296 ◽  
Author(s):  
Kanchan Vishnoi ◽  
Navin Viswakarma ◽  
Ajay Rana ◽  
Basabi Rana
Keyword(s):  
Transcription Factors ◽  
Cancer Progression ◽  
Epithelial Mesenchymal Transition ◽  
Constitutive Expression ◽  
Comprehensive Overview ◽  
Growth And Survival ◽  
Mesenchymal Transition ◽  
Activation Of Transcription ◽  
Target Cancer

Cancer is a multi-step process and requires constitutive expression/activation of transcription factors (TFs) for growth and survival. Many of the TFs reported so far are critical for carcinogenesis. These include pro-inflammatory TFs, hypoxia-inducible factors (HIFs), cell proliferation and epithelial–mesenchymal transition (EMT)-controlling TFs, pluripotency TFs upregulated in cancer stem-like cells, and the nuclear receptors (NRs). Some of those, including HIFs, Myc, ETS-1, and β-catenin, are multifunctional and may regulate multiple other TFs involved in various pro-oncogenic events, including proliferation, survival, metabolism, invasion, and metastasis. High expression of some TFs is also correlated with poor prognosis and chemoresistance, constituting a significant challenge in cancer treatment. Considering the pivotal role of TFs in cancer, there is an urgent need to develop strategies targeting them. Targeting TFs, in combination with other chemotherapeutics, could emerge as a better strategy to target cancer. So far, targeting NRs have shown promising results in improving survival. In this review, we provide a comprehensive overview of the TFs that play a central role in cancer progression, which could be potential therapeutic candidates for developing specific inhibitors. Here, we also discuss the efforts made to target some of those TFs, including NRs.

EPITHELIAL-MESENCHYMAL AND MESENCHYMAL-EPITHELIAL TRANSITION, PATHOGENESIS, REGULATION, THERAPY

2018 ◽  
Vol 64 (1) ◽  
pp. 62-72
Author(s):  
V. Shcherbakov ◽  
T. Ryabichenko ◽  
G. Skosyreva ◽  
A. Trunov
Keyword(s):  
Tumor Growth ◽  
Transforming Growth Factor ◽  
Epithelial Mesenchymal Transition ◽  
Anticancer Therapy ◽  
Lung Carcinogenesis ◽  
Mesenchymal Transition ◽  
Transforming Growth Factor ß1 ◽  
Mesenchymal Epithelial Transition

The review considered the issues of epithelial-mesenchymal transition (EMT) and its role in inflammation, fibrosis, tumor growth. There were analyzed mechanisms and classification of EMT. A comparison of different forms of EMTs was performed. The important role of EMT in the formation of metastasis-initiating cells was noted. There were presented data on the role of fibroblasts in fibrosis of the lung, carcinogenesis. Stimulators and inhibitors of EMTs were summarized. There were considered intracellular paths that were associated with the development of the EMT under the influence of transforming growth factor ß1 (TGF - ß1). It also induced the development of local hypothyroidism, for easy expression of oncofetal genes, which was especially important in tumor growth. Therapy EMT was associated with blocking the actions of TGF - ß1 and was an important area in anticancer therapy.

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