scholarly journals Vimentin as a target for the treatment of COVID-19

2020 ◽  
Vol 7 (1) ◽  
pp. e000623
Author(s):  
Zhenlin Li ◽  
Denise Paulin ◽  
Patrick Lacolley ◽  
Dario Coletti ◽  
Onnik Agbulut
Keyword(s):  
Viral Infection ◽  
Lung Inflammation ◽  
Epithelial To Mesenchymal Transition ◽  
Attachment Site ◽  
Vimentin Expression ◽  
Mesenchymal Transition ◽  
Cellular Target ◽  
Innovative Idea ◽  
Life Threatening ◽  
Approved Drugs

We and others propose vimentin as a possible cellular target for the treatment of COVID-19. This innovative idea is so recent that it requires further attention and debate. The significant role played by vimentin in virus-induced infection however is well established: (1) vimentin has been reported as a co-receptor and/or attachment site for SARS-CoV; (2) vimentin is involved in viral replication in cells; (3) vimentin plays a fundamental role in both the viral infection and the consequent explosive immune-inflammatory response and (4) a lower vimentin expression is associated with the inhibition of epithelial to mesenchymal transition and fibrosis. Moreover, the absence of vimentin in mice makes them resistant to lung injury. Since vimentin has a twofold role in the disease, not only being involved in the viral infection but also in the associated life-threatening lung inflammation, the use of vimentin-targeted drugs may offer a synergistic advantage as compared with other treatments not targeting vimentin. Consequently, we speculate here that drugs which decrease the expression of vimentin can be used for the treatment of patients with COVID-19 and advise that several Food and Drug Administration-approved drugs be immediately tested in clinical trials against SARS-CoV-2, thus broadening therapeutic options for this type of viral infection.

scholarly journals Epithelial-to-Mesenchymal Transition Is Not a Major Modulating Factor in the Cytotoxic Response to Natural Products in Cancer Cell Lines

Molecules ◽  
2021 ◽  
Vol 26 (19) ◽  
pp. 5858
Author(s):  
Baris Kucukkaraduman ◽  
Ekin Gokce Cicek ◽  
Muhammad Waqas Akbar ◽  
Secil Demirkol Canli ◽  
Burcak Vural ◽  
...  
Keyword(s):  
Natural Products ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Epithelial To Mesenchymal Transition ◽  
Epigallocatechin Gallate ◽  
Cancer Cell Lines ◽  
Vimentin Expression ◽  
Mesenchymal Transition ◽  
Urolithin A

Numerous natural products exhibit antiproliferative activity against cancer cells by modulating various biological pathways. In this study, we investigated the potential use of eight natural compounds (apigenin, curcumin, epigallocatechin gallate, fisetin, forskolin, procyanidin B2, resveratrol, urolithin A) and two repurposed agents (fulvestrant and metformin) as chemotherapy enhancers and mesenchymal-to-epithelial (MET) inducers of cancer cells. Screening of these compounds in various colon, breast, and pancreatic cancer cell lines revealed anti-cancer activity for all compounds, with curcumin being the most effective among these in all cell lines. Although some of the natural products were able to induce MET in some cancer cell lines, the MET induction was not related to increased synergy with either 5-FU, irinotecan, gemcitabine, or gefitinib. When synergy was observed, for example with curcumin and irinotecan, this was unrelated to MET induction, as assessed by changes in E-cadherin and vimentin expression. Our results show that MET induction is compound and cell line specific, and that MET is not necessarily related to enhanced chemosensitivity.

The interplay between PD-L1 and vimentin in NSCLC patients: An exploratory analysis.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e20688-e20688
Author(s):  
Giuseppe Bronte ◽  
Maurizio Puccetti ◽  
Paola Cravero ◽  
Sara Ravaioli ◽  
Maria Maddalena Tumedei ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Survival Data ◽  
Immune Modulation ◽  
Epithelial To Mesenchymal Transition ◽  
Immune Escape ◽  
Medical Systems ◽  
Vimentin Expression ◽  
Mesenchymal Transition ◽  
Kaplan Meier ◽  
Nsclc Patients

e20688 Background: The immune modulation is emerging as a key strategy in non-small cell lung cancer (NSCLC) patients management. PD-L1 has been the only biomarker validated for immunotherapy but it holds many limitations. Vimentin is one of the marker for epithelial-to-mesenchymal transition (EMT), a biological process which favors immune escape. We explored two issues: the correlation between PD-L1 and Vimentin expression in NSCLC samples and the prognostic value of PD-L1 and vimentin concordance in NSCLC patients. Methods: We collected all the NSCLC samples evaluable for both PD-L1 and Vimentin and recorded the relative available clinical and survival data, if written informed consent was present. PD-L1 and Vimentin were retrospectively assessed through immunohistochemistry (IHC) by using prediluted antibodies clones SP263 (Ventana Medical Systems, Tucson, AZ, USA) and anti Vimentin V9 (Ventana Medical Systems) on Benchmark XT Platform (Ventana Medical Systems). Biomarker expression was detected and semiquantitatively quantified as the percentage of immunopositive tumor cells on the total of tumor cells. We correlated PD-L1 and Vimentin expression through linear regression. We compared survival of patients with both PD-L1 and Vimentin 0% and all the others via Kaplan-Meier method by using MedCalc software version 18.11.3. Results: Ninety-nine samples underwent PD-L1 and Vimentin IHC analysis. A weak positive statistically significant correlation was found between the 2 biomarkers (r = 0.41; p < 0.001). For 40 patients survival data (from first NSCLC diagnosis) were available. Survival analysis showed that PD-L1 and Vimentin negative patients (n = 12) experienced not statistically significant longer survival (HR = 0.35; 95%CI: 0.08-1.51; p = 0.16). Conclusions: These preliminary findings suggest that an interplay can exist between PD-L1 and vimentin in NSCLC, but analysis in a wider population is necessary. Studies on the significance of this interplay for immunotherapy efficacy should be designed.

scholarly journals Two Faces of TGF-Beta1 in Breast Cancer

2014 ◽  
Vol 2014 ◽  
pp. 1-16 ◽  
Author(s):  
Joanna Magdalena Zarzynska
Keyword(s):  
Breast Cancer ◽  
Cell Cycle Progression ◽  
Epithelial To Mesenchymal Transition ◽  
Current Knowledge ◽  
Clinical Investigation ◽  
Mesenchymal Transition ◽  
Early Stages ◽  
New Therapeutic Approaches ◽  
Genes Encoding ◽  
Life Threatening

Breast cancer (BC) is potentially life-threatening malignancy that still causes high mortality among women. Scientific research in this field is focused on deeper understanding of pathogenesis and progressing of BC, in order to develop relevant diagnosis and improve therapeutic treatment. Multifunctional cytokine TGF-β1 is one of many factors that have a direct influence on BC pathophysiology. Expression of TGF-β1, induction of canonical and noncanonical signaling pathways, and mutations in genes encoding TGF-β1 and its receptors are correlated with oncogenic activity of this cytokine. In early stages of BC this cytokine inhibits epithelial cell cycle progression and promotes apoptosis, showing tumor suppressive effects. However, in late stages, TGF-β1 is linked with increased tumor progression, higher cell motility, cancer invasiveness, and metastasis. It is also involved in cancer microenvironment modification and promotion of epithelial to mesenchymal transition (EMT). This review summarizes the current knowledge on the phenomenon called “TGF-β1 paradox”, showing that better understanding of TGF-β1 functions can be a step towards development of new therapeutic approaches. According to current knowledge several drugs against TGF-β1 have been developed and are either in nonclinical or in early stages of clinical investigation.

scholarly journals Human Peripheral Blood-derived Mast Cells Contribute to Epithelial to Mesenchymal Transition in Bronchial Epithelial Cells in the Presence of IL-1β

2020 ◽  
Author(s):  
Xian-Song Wang ◽  
Li Xie ◽  
Kaiyu Zheng
Keyword(s):  
Mast Cells ◽  
Peripheral Blood ◽  
Epithelial To Mesenchymal Transition ◽  
Human Peripheral Blood ◽  
Cell Junctions ◽  
Vimentin Expression ◽  
Bronchial Epithelial ◽  
Mesenchymal Transition ◽  
Tgf Β1 ◽  
E Cadherin

Abstract Background: Bronchial epithelial to mesenchymal transition （EMT）is an important mechanism for the airway remodeling in asthmatics. Mast cell is one of the critical effector cells in pathogenesis of asthma. Although mast cells have been shown to release a plethora of pro-fibrotic factors with the potential to induce EMT, it is not clear whether mast cells also directly have an impact on the bronchial EMT. In this study, we investigated the contribution of human mast cells to EMT in human bronchial epithelial cell line 16-HBE. Methods: Human peripheral blood-derived mast cells were co-cultured with 16-HBE cells. The protein and mRNA expression of E-cadherin and vimentin in 16-HBE cells were analyzed by Western blot and quantitative real-time PCR. A scratch wound assay was performed to evaluate the migratory properties of the 16-HBE cells.Results: Mast cells alone failed to produce significant effects on the epithelial morphology, mobility, and expression of E-cadherin and vimentin. However, mast cells in combination of interleukin (IL)-1β significantly decreased E-cadherin expression but increased vimentin expression in the co-cultured 16-HBE cells, which exhibited a spindle-like appearance with reduced cell junctions and enhanced migration. The down-regulation of E-cadherin expression and up-regulation of vimentin expression were not abrogated by the transforming growth factor (TGF)-β1 neutralizing antibody.Conclusion: Mast cells combined with IL-1β, not mast cells alone, were able to induce EMT in 16-HBE cells through a TGF-β1-independent mechanism. The results of in vitro culture suggest the possibility that mast cells contribute to human bronchial epithelial EMT in the asthmatic airway tissues with high level of IL-1β.

scholarly journals Pharmacologic Targeting of BET Proteins Attenuates Hyperuricemic Nephropathy in Rats

2021 ◽  
Vol 12 ◽  
Author(s):  
Chongxiang Xiong ◽  
Jin Deng ◽  
Xin Wang ◽  
Xiaofei Shao ◽  
Qin Zhou ◽  
...  
Keyword(s):  
Uric Acid ◽  
Epithelial To Mesenchymal Transition ◽  
Organic Anion ◽  
Mesenchymal Cell ◽  
Serum Levels ◽  
Organic Anion Transporter ◽  
Vimentin Expression ◽  
Mesenchymal Transition ◽  
Expression Levels ◽  
Anion Transporter

Hyperuricemia is an independent risk factor for renal damage and promotes the progression of chronic kidney disease. In this study, we investigated the effect of I-BET151, a small-molecule inhibitor targeting the bromodomain and extraterminal (BET) proteins, on the development of hyperuricemic nephropathy (HN), and the mechanisms involved. Expression levels of bromodomain-containing protein 2 and 4, but not 3 were increased in the kidney of rats with HN; administration of I-BET151 effectively prevented renal dysfunction, decreased urine microalbumin, and attenuated renal fibrosis as indicated by reduced activation of renal interstitial fibroblasts and expression of fibronectin and collagen I in HN rats. Mechanistic studies show that I-BET151 treatment inhibited transition of renal epithelial cells to a mesenchymal cell type as evidenced by preservation of E-cadherin and reduction of vimentin expression. This was coincident with reduced expression of TGF-β1 and dephosphorylation of Smad3 and ERK1/2. I-BET151 was also effective in inhibiting phosphorylation of NF-κB, expression of multiple cytokines and chemokines, and infiltration of macrophages to the injured kidney. Although there were increased serum levels of uric acid and xanthine oxidase, an enzyme that catalyzes production of uric acid, and decreased expression of renal organic anion transporter 1 and 3 that promote urate excretion in the model of HN, and reduced expression levels of urine uric acid, I-BET151 treatment did not affect these responses. Collectively, our results indicate that I-BET151 alleviates HN by inhibiting epithelial to mesenchymal transition and inflammation in association with blockade of TGF-β, ERK1/2 and NF-κB signaling.

scholarly journals Sex-dependent gene co-expression in the human body

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Robin J. G. Hartman ◽  
Michal Mokry ◽  
Gerard Pasterkamp ◽  
Hester M. den Ruijter
Keyword(s):  
Sex Differences ◽  
Human Body ◽  
Gene Networks ◽  
Epithelial To Mesenchymal Transition ◽  
Tissue Expression ◽  
Whole Body ◽  
Sequencing Data ◽  
Disease Etiology ◽  
Mesenchymal Transition ◽  
Approved Drugs

AbstractMany pathophysiological mechanisms in human health and disease are dependent on sex. Systems biology approaches are successfully used to decipher human disease etiology, yet the effect of sex on gene network biology is mostly unknown. To address this, we used RNA-sequencing data of over 700 individuals spanning 24 tissues from the Genotype-Tissue Expression project to generate a whole-body gene co-expression map and quantified the sex differences per tissue. We found that of the 13,787 genes analyzed in 24 tissues, 29.5% of the gene co-expression is influenced by sex. For example, skeletal muscle was predominantly enriched with genes co-expressed stronger in males, whereas thyroid primarily contained genes co-expressed stronger in females. This was accompanied by consistent sex differences in pathway enrichment, including hypoxia, epithelial-to-mesenchymal transition, and inflammation over the human body. Furthermore, multi-organ analyses revealed consistent sex-dependent gene co-expression over numerous tissues which was accompanied by enrichment of transcription factor binding motifs in the promoters of these genes. Finally, we show that many sex-biased genes are associated with sex-biased diseases, such as autoimmunity and cancer, and more often the target of FDA-approved drugs than non-sexbiased genes. Our study suggests that sex affects biological gene networks by differences in gene co-expression and that attention to the effect of sex on biological responses to medical drugs is warranted.

scholarly journals Hedgehog signaling activation required for glypican-6-mediated regulation of invasion, migration, and epithelial–mesenchymal transition of gastric cancer cells

2020 ◽  
Vol 40 (6) ◽  
Author(s):  
Chen Zeng ◽  
Ran Yan ◽  
Guanghua Yang ◽  
Sen Xiang ◽  
Fuli Zhao
Keyword(s):  
Gastric Cancer ◽  
Hedgehog Signaling ◽  
Epithelial To Mesenchymal Transition ◽  
Epithelial Mesenchymal Transition ◽  
Migration And Invasion ◽  
Epithelial Cell Line ◽  
Gastric Cancer Cells ◽  
Vimentin Expression ◽  
Mesenchymal Transition ◽  
Signaling Activation

Abstract Gastric cancer (GC) is the fifth most common cancer worldwide and one of the most aggressive cancers in China. Glypican 6 is highly expressed in gastric adenocarcinoma and may act as a diagnostic and prognostic marker; however, the functional importance and molecular mechanism of glypican 6 in GC remains unclear. In the current study, we aimed to reveal the function and mechanism of glypican 6 in two GC cell lines: MKN-45 and SGC-7901. We found higher expression of glypican 6 in MKN-45 and SGC-7901 cells than in cells from the normal gastric mucosa epithelial cell line GES-1. Glypican 6 knockdown suppressed MKN-45 and SGC-7901 cell proliferation. A Transwell assay confirmed that glypican 6 silencing inhibited the migration and invasiveness of MKN-45 and SGC-7901 cells. Epithelial-to-mesenchymal transition (EMT) markers were determined by western blotting, and the results showed reduced Vimentin expression and elevated E-cadherin expression in glypican 6 short interfering RNA (siRNA) transfected MKN-45 and SGC-7901 cells. However, glypican 6 overexpression in GES-1 cells showed no significant promotion on GES-1 cells proliferation and migration. Further studies confirmed that glypican 6 siRNA regulated Hedgehog and Gli1 signaling and participated in the function of glypican 6 on MKN-45 and SGC-7901 cell migration and invasion. Our findings suggest that decreased glypican 6 expression inhibits the migration and invasion ability of GC cells.

Crosstalk of long non-coding RNAs and EMT: Searching the missing pieces of an incomplete puzzle for lung cancer therapy

2021 ◽  
Vol 21 ◽  
Author(s):  
Milad Ashrafizadeh ◽  
Md Shahinozzaman ◽  
Sima Orouei ◽  
Vahideh Zarrin ◽  
Kiavash Hushmandi ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Therapy ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Epithelial To Mesenchymal Transition ◽  
Lung Cancer Cells ◽  
Mesenchymal Transition ◽  
Life Threatening ◽  
Non Coding Rnas ◽  
Potential Factors

Background: Lung cancer is considered to be the first place among the cancer-related deaths worldwide and demands novel strategies in the treatment of this life-threatening disorder. The aim of this review is to explore regulation of epithelial-to-mesenchymal transition (EMT) by long non-coding RNAs (lncRNAs) in lung cancer. Introduction: LncRNAs can be considered as potential factors for targeting in cancer therapy, since they regulate a bunch of biological processes, e.g. cell proliferation, differentiation and apoptosis. The abnormal expression of lncRNAs occurs in different cancer cells. On the other hand, epithelial-to-mesenchymal transition (EMT) is a critical mechanism participating in migration and metastasis of cancer cells. Method: Different databases including Googlescholar, Pubmed and Sciencedirect were used for collecting articles using keywords such as “LncRNA”, “EMT”, and “Lung cancer”. Result: There are tumor-suppressing lncRNAs that can suppress EMT and metastasis of lung cancer cells. Expression of such lncRNAs undergoes down-regulation in lung cancer progression and restoring their expression is of importance in suppressing lung cancer migration. There are tumor-promoting lncRNAs triggering EMT in lung cancer and enhancing their migration. Conclusion: LncRNAs are potential regulators of EMT in lung cancer, and targeting them, both pharmacologically and genetically, can be of importance in controlling migration of lung cancer cells.

scholarly journals Role of microRNA/Epithelial-to-Mesenchymal Transition Axis in the Metastasis of Bladder Cancer

Biomolecules ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. 1159
Author(s):  
Milad Ashrafizadeh ◽  
Kiavash Hushmandi ◽  
Mehrdad Hashemi ◽  
Mohammad Esmaeil Akbari ◽  
Peter Kubatka ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Transforming Growth Factor Beta ◽  
Epithelial To Mesenchymal Transition ◽  
Transforming Growth Factor ◽  
Molecular Pathways ◽  
Mesenchymal Transition ◽  
Cellular Events ◽  
Number Of Factors ◽  
Life Threatening

Bladder cancer (BC) is the 11th most common diagnosed cancer, and a number of factors including environmental and genetic ones participate in BC development. Metastasis of BC cells into neighboring and distant tissues significantly reduces overall survival of patients with this life-threatening disorder. Recently, studies have focused on revealing molecular pathways involved in metastasis of BC cells, and in this review, we focus on microRNAs (miRNAs) and their regulatory effect on epithelial-to-mesenchymal transition (EMT) mechanisms that can regulate metastasis. EMT is a vital process for migration of BC cells, and inhibition of this mechanism restricts invasion of BC cells. MiRNAs are endogenous non-coding RNAs with 19–24 nucleotides capable of regulating different cellular events, and EMT is one of them. In BC cells, miRNAs are able to both induce and/or inhibit EMT. For regulation of EMT, miRNAs affect different molecular pathways such as transforming growth factor-beta (TGF-β), Snail, Slug, ZEB1/2, CD44, NSBP1, which are, discussed in detail this review. Besides, miRNA/EMT axis can also be regulated by upstream mediators such as lncRNAs, circRNAs and targeted by diverse anti-tumor agents. These topics are also discussed here to reveal diverse molecular pathways involved in migration of BC cells and strategies to target them to develop effective therapeutics.

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