scholarly journals Epithelial–Mesenchymal Transition Gene Signature Related to Prognostic in Colon Adenocarcinoma

2021 ◽  
Vol 11 (6) ◽  
pp. 476
Author(s):  
Constantin Busuioc ◽  
Cristina Alexandra Ciocan-Cartita ◽  
Cornelia Braicu ◽  
Oana Zanoaga ◽  
Lajos Raduly ◽  
...  
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
Colon Adenocarcinoma ◽  
Gene Signature ◽  
Metastatic Phenotype ◽  
Mesenchymal Transition ◽  
Qrt Pcr ◽  
Recurrence Prediction ◽  
Tumor Tissues ◽  
Public Datasets ◽  
Related Mortality

Colon adenocarcinoma (COAD) remains an important cause of cancer-related mortality worldwide. Epithelial–mesenchymal transition (EMT) is a key mechanism, promoting not only the invasive or metastatic phenotype but also resistance to therapy. Using bioinformatics approaches, we studied the alteration on EMT related genes and its implication on COAD prognostic based on public datasets. For the EMT mechanisms, two overexpressed genes were identified (NOX4 and IGF2BP3), as well as five downregulated genes (BMP5, DACT3, EEF1A2, GCNT2 and SFRP1) that were related to prognosis in COAD. A qRT-PCR validation step was conducted in a COAD patient cohort comprising of 29 tumor tissues and 29 normal adjacent tissues, endorsing the expression level for BMP5, as well as for two of the miRNAs targeting key EMT related genes, revealing upregulation of miR-27a-5p and miR-146a-5p. The EMT signature can be used to develop a panel of biomarkers for recurrence prediction in COAD patients, which may contribute to the improvement of risk stratification for the patients.

scholarly journals An epithelial-mesenchymal transition-related 5-gene signature predicting the prognosis of hepatocellular carcinoma patients

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Gongmin Zhu ◽  
Hongwei Xia ◽  
Qiulin Tang ◽  
Feng Bi
Keyword(s):  
Tumor Metastasis ◽  
Cox Regression ◽  
Epithelial Mesenchymal Transition ◽  
Risk Group ◽  
Gene Signature ◽  
High Risk Group ◽  
Related Gene ◽  
Mesenchymal Transition ◽  
Cox Regression Analysis ◽  
Qrt Pcr

Abstract Background Tumor metastasis is one of the leading reasons of the dismal prognosis of hepatocellular carcinoma (HCC). Epithelial-mesenchymal transition (EMT) is closely associated with tumor metastasis including HCC. The purpose of this study is to construct and validate an EMT-related gene signature for predicting the prognosis of HCC patients. Methods Gene expression data of HCC patients was downloaded from The Cancer Genome Atlas (TCGA) database. Gene set enrichment analysis (GSEA) was performed to found the EMT-related gene sets which were obviously distinct between normal samples and paired HCC samples. Cox regression analysis was used to develop an EMT-related prognostic signature, and the performance of the signature was evaluated by Kaplan–Meier curves and time-dependent receiver operating characteristic (ROC) curves. A nomogram incorporating the independent predictors was established. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression levels of the hub genes in HCC cell lines, and the role of PDCD6 in the metastasis of HCC was determined by functional experiments. Results An EMT-related 5-gene signature (PDCD6, TCOF1, TRIM28, EZH2 and FAM83D) was constructed using univariate and multivariate Cox regression analysis. Based on the signature, the HCC patients were classified into high- and low-risk groups, and patients in high-risk group had a poor prognosis. Time-dependent ROC and Cox regression analyses suggested that the signature could predict HCC prognosis exactly and independently. The predictive capacity of the signature was also validated in two external cohorts. GSEA results showed that many cancer-related signaling pathways such as PI3K/Akt/mTOR pathway and TGF-β/SMAD pathway were enriched in high-risk group. The result of qRT-PCR revealed that PDCD6, TCOF1 and FAM83D were highly expressed in HCC cancer cells. Among them, PDCD6 were found to promote cell migration and invasion. Conclusion The EMT-related 5-gene signature can serve as a promising prognostic biomarker for HCC patients and may provide a novel mechanism of HCC metastasis.

scholarly journals Oxidized Phospholipids in Tumor Microenvironment Stimulate Tumor Metastasis via Regulation of Autophagy

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 558
Author(s):  
Jin Kyung Seok ◽  
Eun-Hee Hong ◽  
Gabsik Yang ◽  
Hye Eun Lee ◽  
Sin-Eun Kim ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Cancer Cells ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Migration And Invasion ◽  
Autophagic Flux ◽  
Oxidized Phospholipids ◽  
Mcf7 Cells ◽  
Mesenchymal Transition ◽  
Tumor Tissues

Oxidized phospholipids are well known to play physiological and pathological roles in regulating cellular homeostasis and disease progression. However, their role in cancer metastasis has not been entirely understood. In this study, effects of oxidized phosphatidylcholines such as 1-palmitoyl-2-(5-oxovaleroyl)-sn-glycero-3-phosphocholine (POVPC) on epithelial-mesenchymal transition (EMT) and autophagy were determined in cancer cells by immunoblotting and confocal analysis. Metastasis was analyzed by a scratch wound assay and a transwell migration/invasion assay. The concentrations of POVPC and 1-palmitoyl-2-glutaroyl-sn-glycero-phosphocholine (PGPC) in tumor tissues obtained from patients were measured by LC-MS/MS analysis. POVPC induced EMT, resulting in increase of migration and invasion of human hepatocellular carcinoma cells (HepG2) and human breast cancer cells (MCF7). POVPC induced autophagic flux through AMPK-mTOR pathway. Pharmacological inhibition or siRNA knockdown of autophagy decreased migration and invasion of POVPC-treated HepG2 and MCF7 cells. POVPC and PGPC levels were greatly increased at stage II of patient-derived intrahepatic cholangiocarcinoma tissues. PGPC levels were higher in malignant breast tumor tissues than in adjacent nontumor tissues. The results show that oxidized phosphatidylcholines increase metastatic potential of cancer cells by promoting EMT, mediated through autophagy. These suggest the positive regulatory role of oxidized phospholipids accumulated in tumor microenvironment in the regulation of tumorigenesis and metastasis.

scholarly journals Western diet leads to aging-related tumorigenesis via activation of the inflammatory, UPR, and EMT pathways

2021 ◽  
Vol 12 (7) ◽  
Author(s):  
Ricardo Imbroisi Filho ◽  
Alan C. Ochioni ◽  
Amanda M. Esteves ◽  
João G. B. Leandro ◽  
Thainá M. Demaria ◽  
...  
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
Tumor Development ◽  
Western Diet ◽  
Mesenchymal Transition ◽  
Akt Phosphorylation ◽  
Unfolded Protein ◽  
Tissue Microenvironment ◽  
Tumor Tissues ◽  
Causative Factors ◽  
Protein Response

AbstractAmong the principal causative factors for the development of complications related to aging is a diet rich in fats and sugars, also known as the Western diet. This diet advocates numerous changes that might increase the susceptibility to initiate cancer and/or to create a tissue microenvironment more conducive to the growth of malignant cells, thus favoring the progression of cancer and metastasis. Hypercaloric diets in general lead to oxidative stress generating reactive oxygen species and induce endoplasmic reticulum stress. Our results demonstrate that mice bearing tumors fed with a Western diet presented bigger tumor mass with increased insulin sensitivity in these tissues. Several markers of insulin signaling, such as AKT phosphorylation and mTOR pathway, are promoted in tumors of Western diet-fed animals. This process is associated with increased macrophage infiltration, activation of unfolded protein response pathway, and initiation of epithelial–mesenchymal transition (EMT) process in these tumor tissues. Summing up, we propose that the Western diet accelerates the aging-related processes favoring tumor development.

scholarly journals Integrin β4 as a Potential Diagnostic and Therapeutic Tumor Marker

Biomolecules ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1197
Author(s):  
Haoyu Yang ◽  
Zixuan Xu ◽  
Yuqian Peng ◽  
Jiali Wang ◽  
Yang Xiang
Keyword(s):  
Signal Transduction ◽  
Tumor Marker ◽  
Tumor Invasion ◽  
Epithelial Mesenchymal Transition ◽  
Vital Role ◽  
Structure And Function ◽  
Mesenchymal Transition ◽  
Tumor Tissues ◽  
Integrin Β4 ◽  
And Function

Integrin β4 (ITGβ4) is a class of transmembrane adhesion molecules composed of hemidesmosomes (HDs). Its unique long intracellular domain provides intricate signal transduction functions. These signal transduction effects are especially prominent in tumors. Many recent studies have shown that integrin β4 is differentially expressed in various tumors, and it plays a vital role in tumor invasion, proliferation, epithelial–mesenchymal transition, and angiogenesis. Therefore, we categorize the research related to integrin β4, starting from its structure and function in tumor tissues, and provide a basic description. Based on its structure and function, we believe that integrin β4 can be used as a tumor marker. In clinical practice, it is described as a diagnostic marker for the targeted treatment of cancer and will be helpful in the clinical diagnosis and treatment of tumors.

scholarly journals Identification of a Novel Epithelial-Mesenchymal Transition Gene Signature Regulated by KEAP1-NRF2 Pathway in Esophageal Carcinoma

2020 ◽  
Author(s):  
Mohamed Elshaer ◽  
Ahmed Hammad ◽  
Xiu Jun Wang ◽  
Xiuwen Tang
Keyword(s):  
Cell Lines ◽  
Epithelial Mesenchymal Transition ◽  
Cancer Cell Line ◽  
Enrichment Analysis ◽  
Gene Signature ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Mesenchymal Transition ◽  
Gene Set ◽  
Over Expression

Abstract BackgroundKEAP1-NRF2 pathway alterations were identified in many cancers including, esophageal cancer (ESCA). Identifying biomarkers that are associated with mutations in this pathway will aid in defining this cancer subset; and hence in supporting precision and personalized medicine. MethodsIn this study, 182 tumor samples from the Cancer Genome Atlas (TCGA)-ESCA RNA-Seq V2 level 3 data were segregated into two groups KEAP1-NRF2-mutated (22) and wild-type (160).The two groups were subjected to differential gene expression analysis, and we performed Gene Set Enrichment Analysis (GSEA) to determine all significantly affected biological pathways. Then, the enriched gene set was integrated with the differentially expressed genes (DEGs) to identify a gene signature regulated by the KEAP1-NRF2 pathway in ESCA. Furthermore, we validated the gene signature using mRNA expression data of ESCA cell lines provided by the Cancer Cell Line Encyclopedia (CCLE). The identified signature was tested in 3 independent ESCA datasets to assess its prognostic value.ResultsWe identified 11 epithelial-mesenchymal transition (EMT) genes regulated by the KEAP1-NRF2 pathway in ESCA patients. Five of the 11 genes showed significant over-expression in KEAP1-NRF2-mutated ESCA cell lines. In addition, the over-expression of these five genes was significantly associated with poor survival in 3 independent ESCA datasets, including the TCGA-ESCA dataset.ConclusionAltogether, we identified a novel EMT 5-gene signature regulated by the KEAP1-NRF2 axis and this signature is strongly associated with metastasis and drug resistance in ESCA. These 5-genes are potential biomarkers and therapeutic targets for ESCA patients in whom the KEAP1-NRF2 pathway is altered.

scholarly journals Human Cancer Cells Express Slug-based Epithelial-Mesenchymal Transition Gene Signature Obtained in Vivo

2011 ◽  
Author(s):  
Jessica Kandel ◽  
Dimitris Anastassiou ◽  
Viktoria Rumjantseva ◽  
Wei-yi Cheng ◽  
Jianzhong Huang ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Human Cancer ◽  
Gene Signature ◽  
Mesenchymal Transition ◽  
Human Cancer Cells

scholarly journals Mechanotransduction in tumor progression: The dark side of the force

2018 ◽  
Vol 217 (5) ◽  
pp. 1571-1587 ◽  
Author(s):  
Florence Broders-Bondon ◽  
Thanh Huong Nguyen Ho-Bouldoires ◽  
Maria-Elena Fernandez-Sanchez ◽  
Emmanuel Farge
Keyword(s):  
Cell Cycle ◽  
Conformational Changes ◽  
Molecular Mechanisms ◽  
Epithelial Mesenchymal Transition ◽  
Hydrodynamic Pressure ◽  
Dark Side ◽  
Mesenchymal Transition ◽  
Biochemical Pathways ◽  
Protein Conformational Changes ◽  
Tumor Tissues

Cancer has been characterized as a genetic disease, associated with mutations that cause pathological alterations of the cell cycle, adhesion, or invasive motility. Recently, the importance of the anomalous mechanical properties of tumor tissues, which activate tumorigenic biochemical pathways, has become apparent. This mechanical induction in tumors appears to consist of the destabilization of adult tissue homeostasis as a result of the reactivation of embryonic developmental mechanosensitive pathways in response to pathological mechanical strains. These strains occur in many forms, for example, hypervascularization in late tumors leads to high static hydrodynamic pressure that can promote malignant progression through hypoxia or anomalous interstitial liquid and blood flow. The high stiffness of tumors directly induces the mechanical activation of biochemical pathways enhancing the cell cycle, epithelial–mesenchymal transition, and cell motility. Furthermore, increases in solid-stress pressure associated with cell hyperproliferation activate tumorigenic pathways in the healthy epithelial cells compressed by the neighboring tumor. The underlying molecular mechanisms of the translation of a mechanical signal into a tumor inducing biochemical signal are based on mechanically induced protein conformational changes that activate classical tumorigenic signaling pathways. Understanding these mechanisms will be important for the development of innovative treatments to target such mechanical anomalies in cancer.

scholarly journals BTBD7 Downregulates E-Cadherin and Promotes Epithelial-Mesenchymal Transition in Lung Cancer

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Jie Shu ◽  
Lin Wang ◽  
Fei Han ◽  
Yubin Chen ◽  
Shunjun Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Western Blotting ◽  
Nude Mice ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
A549 Cells ◽  
Migration Ability ◽  
Mesenchymal Transition ◽  
Qrt Pcr ◽  
E Cadherin

Metastasis is the leading cause of lung cancer-associated death. Downregulated expression of E-cadherin followed by epithelial-mesenchymal transition (EMT) is critical for metastasis initiation in lung cancer. BTBD7 plays essential roles in lung cancer metastasis, but the mechanisms remain unknown. This study aimed to investigate the relationship between BTBD7 and E-cadherin in lung cancer and explore the role of BTBD7 in EMT. Fresh lung cancer and paracancer tissue specimens were collected from 30 patients, and the expression of BTBD7, E-cadherin, N-cadherin, fibronectin, and vimentin was analyzed by qRT-PCR, western blotting, and immunohistochemistry. A549 and HBE cells were cultured and treated with TGF-β1 for 72 h to induce EMT. Western blotting and qRT-PCR were performed to evaluate the expression of BTBD7, E-cadherin, N-cadherin, fibronectin, and vimentin. Then, A549 cells were treated separately with the BTBD7-ENTER plasmid, BTBD7-siRNA, and paclitaxel. After TGF-β1-induced EMT, the abovementioned markers were analyzed by western blotting and qRT-PCR. Wound healing assays were applied to assess the migration ability of cells in different groups. For animal experiments, A549 cells transfected with the BTBD7-ENTER plasmid were transplanted into BALB/c nude mice. After 4 weeks, all nude mice were sacrificed, and tumor tissues were harvested for qRT-PCR, western blot, and immunohistochemical analyses of the abovementioned markers. All experimental results showed that the levels of BTBD7, N-cadherin, fibronectin, and vimentin were increased in lung cancer tissues and cells, while the E-cadherin level was decreased. Transfection experiments showed that BTBD7 inhibited E-cadherin expression and enhanced EMT. Moreover, the migration capacity of lung cancer cells was increased by the high level of BTBD7. We concluded that BTBD7 is highly expressed during lung cancer development and metastasis and can inhibit the expression of E-cadherin and promote EMT in lung cancer. BTBD7 may thus be a therapeutic target for lung cancer.

scholarly journals A Six-Epithelial–Mesenchymal Transition Gene Signature May Predict Metastasis of Triple-Negative Breast Cancer

2020 ◽  
Vol Volume 13 ◽  
pp. 6497-6509
Author(s):  
Li Yuan Wei ◽  
Xiao Jun Zhang ◽  
Li Wang ◽  
Li Na Hu ◽  
Xu Dong Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Epithelial Mesenchymal Transition ◽  
Gene Signature ◽  
Mesenchymal Transition

Long noncoding RNA XIST regulates the EGF receptor to promote TGF-β1-induced epithelial–mesenchymal transition in pancreatic cancer

2020 ◽  
Vol 98 (2) ◽  
pp. 267-276 ◽  
Author(s):  
Lei Zou ◽  
Feng-Rong Chen ◽  
Ren-Pin Xia ◽  
Hua-Wei Wang ◽  
Zhen-Rong Xie ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cell Proliferation ◽  
Growth Factor ◽  
Epithelial Mesenchymal Transition ◽  
Luciferase Reporter ◽  
Mesenchymal Transition ◽  
Clinical Specimens ◽  
Qrt Pcr ◽  
Reporter Assays ◽  
Tgf Β1

Background: This study focuses on the lncRNA XIST (X inactive-specific transcript), an lncRNA involved in multiple human cancers, and investigates the functional significance of XIST and the molecular mechanisms underlying the epithelial–mesenchymal transition (EMT) in pancreatic cancer (PC). Methods: Clinical specimens from 25 patients as well as 5 human PC cell lines were analyzed for XIST, YAP, and microRNA(miR)-34a by quantitative real-time PCR (qRT-PCR) and immunohistochemistry. To investigate how XIST influences cell proliferation, invasiveness, and apoptosis in PC, we performed the CCK-8 assays, Transwell assays, and flow cytometry. Luciferase reporter assays, qRT-PCR, and Western blot were applied to prove that miR-34a directly binds to XIST. Results: Up-regulation of XIST and Yes associated protein (YAP) and down-regulation of miR-34a were consistently observed in the clinical specimens and PC cell lines. Silencing XIST reduced the expression of YAP and suppressed transforming growth factor (TGF)-β1-induced EMT, while over-expression of XIST increased the expression of YAP and promoted EMT. In addition, inhibition of epidermal growth factor receptor (EGFR) hampered the XIST-promoted EMT. The results from the luciferase reporter assays confirmed that miR-34a directly targets XIST and suggested that XIST regulates cell proliferation, invasiveness, and apoptosis in PC by sponging miR-34a. Conclusions: XIST promotes TGF-β1-induced EMT by regulating the miR-34a–YAP–EGFR axis in PC.

Sign in / Sign up

Export Citation Format

Share Document