Browsing by Subject "EMT"

Now showing 1 - 11 of 11
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    A twist tale of cancer metastasis and tumor angiogenesis
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2015) Tseng, Jen-Chieh; Chen, Hsiao-Fan; Wu, Kou-Juey
    Twist1 is an evolutionally conserved transcription factor. Originally identified in Drosophila as a key regulator for mesoderm development, it was later implicated in many human diseases, including Saethre-Chotzen syndrome and cancer. Twist1’s involvement in cancer has been well recognized. Driven by hypoxia-induced factor-1 (HIF-1), Twist1 has been considered as a proto-oncogene and its overexpression has been observed in a wide variety of human cancers. High expression level of Twist1 is closely related to tumor aggressiveness and metastatic potential. In cancer cells, Twist1 has been shown to function as a key regulator of epithelial-mesenchymal transition (EMT), a critical process for metastasis initiation. Twist1 has also been implicated in maintaining cancer stemness for selfrenewal and chemoresistance. This review first summarizes the roles of Twist1 in embryo development and Saethre-Chotzen syndrome followed by a discussion of Twist1’s critical functions in cancer. In particular, the review focuses on the recent discovery of Twist1’s capability to promote endothelial transdifferentiation of cancer cells beyond EMT.
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    An immunohistochemical study of NFE2L2, KEAP1 and 8-hydroxy-2'-deoxyguanosine and the EMT markers SNAI2, ZEB1 and TWIST1 in metastatic melanoma
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2017) Hintsala, Hanna Riikka; Haapasaari, Kirsi Maria; Soini, Ylermi; Karihtala, Peeter
    Background: Little is known regarding the role of redox balance regulators in metastatic melanomas, but there is some evidence for a link between epithelial-to-mesenchymal transition (EMT) and cellular redox status. Methods: We compared the immunohistochemical expression of nuclear factor erythroid-2-related factor 2 (NFE2L2), Kelch-like ECH-associated protein 1 (KEAP1), 8-hydroxy-2'-deoxyguanosine (8-OHdG), TWIST1, SNAI2 and ZEB1 between primary melanomas and metastases in a cohort of 23 nevi, 66 malignant melanomas and 22 metastases. Results: Nuclear NFE2L2 expression was higher (p=0.003) and cytoplasmic KEAP1 lower (p=0.026) in metastatic lesions than at primary sites. Nuclear NFE2L2 expression was associated with the presence of distant metastases (p=0.040) and with nuclear TWIST1 expression (p=0.002). Patients having both NFE2L2 and TWIST1 expression in nuclei had an extremely poor prognosis (p=0.0003). In multivariate analysis nuclear TWIST1 expression was an independent predictor of a poorer prognosis (HR 2.99, 95% CI 1.17-7.69; p=0.023) and the invasive TWIST1/ZEB1 phenotype showed poorer melanoma-specific survival (HR 7.28, 95% CI 2.23-23.77; p=0.001). Nuclear expression of 8-OHdG (p=0.001) was lower at metastatic sites than in primary lesions. Conclusions: EMT signalling and the KEAP1/NFE2L2- axis are likely to be involved in metastatic spread of malignant melanoma and also appear to have potential interactions.
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    BATF is involved in the malignant phenotype and epithelial-mesenchymal transition of colon cancer cells via ERK/PD-L1 signaling
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2025) Chen, Xiaoqiong; Dong, Huaqian; Jin, Liping
    Objective. Transcription factors have emerged as primary regulators in colon cancer. Basic Leucine Zipper Transcription Factor (BATF) was found to be differentially expressed in colon cancer. This study aimed to explore the impact of BATF on the malignant phenotype and epithelial-mesenchymal transition (EMT) process. Methods. Based on The Cancer Genome Atlas (TCGA) data, the correlation between BATF and patients’ overall prognosis was analyzed. BATF expression in epithelial and colon cancer cells was evaluated. By knocking down its levels in colon cancer cells, its effects on the malignant phenotype, apoptosis, EMT progression, and ERK/PD-L1 were evaluated. Cells were treated with ERK/PD-L1 agonists, and the BATF cell regulation was re-examined. Results. BATF levels were negatively correlated with patients’ overall survival. BATF is upregulated in colon cancer cell lines, and BATF knockdown in HCT116 cells suppressed the malignant cellular phenotypes (proliferation, migration, and invasion) and increased apoptosis. BATF knockdown inhibited EMT and ERK/PD-L1 signaling activation, whereas upon agonist treatment, BATF potency was disrupted. Conclusion. This study revealed that BATF is involved in the malignant phenotype and EMT of colon cancer cells, and this process may be mediated by ERK/PD-L1 signaling
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    Carcinosarcomas: tumors in transition?
    (F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2015) Somarelli, Jason A.; Boss, Mary-Keara; Epstein, Jonathan I.; Armstrong, Andrew J.; Garcia-Blanco, Mariano A.
    Carcinosarcomas are rare, biphasic tumors that are comprised of carcinomatous and sarcomatous elements. While the exact mechanism by which these two phenotypes arise within a single tumor remains unclear, molecular evidence indicates that the epitheliod and spindle-cell components share a clonal origin. We propose that the biphasic nature of these neoplasms may represent an extreme case of epithelial plasticity, in which an epithelial-like cell undergoes a transition to a more mesenchymal phenotype. The present review will discuss both the histological and molecular biological evidence of the involvement of epithelial plasticity in driving the mixed phenotypes observed in carcinosarcomas.
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    Downregulation of desmoglein 2 promotes EMT progression in gallbladder cancer
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Wang, LingLing; Lv, You; Li, JinBin; Nan, YongShan; Piao, LongZhen; Liang, ZheLong
    Objective. To explore the correlation between the expression level of Desmoglein 2 (DSG2) and the epithelial-mesenchymal transition (EMT) progression in gallbladder cancer (GBC). Method. 106 GBC tissue specimens and corresponding clinical information were collected to make a tissue microarray. Immunohistochemical method was used to test the expression level of DSG2 in GBC tissues. DSG2 was knocked down in the GBC cell line GBC-SD to detect the change of its invasion and metastasis ability. Then RT-qPCR and Western Blot were applied on the DSG2-knocked down GBC-SD cells to detect the expression level change of genes associated with EMT. Result. The high expression rate of DSG2 was significantly correlated with the N, M and TNM staging of patients (P<0.05). Survival analysis identified that GBC patients with high DSG2 expression level had significantly better survival (P<0.05). To further investigate the potential mechanism of DSG2 on regulating GBC tumor progression, we used knockdown DSG2 on GBC-SD cell lines. The results showed that GBC-SD cell lines with DSG2 knockdown showed a promotion of cell invasion and metastatic ability. The mRNA levels of EMT-related genes E-Cadherin, Snail, Twist, ZEB1, and β-catenin, which is a key protein in the Wnt signaling pathway, were also significantly altered. Besides, protein levels of E-cadherin and Snail showed consistent results. Conclusion. The downregulation of DSG2 in gallbladder cancer is hypothesized to be associated with the invasion and metastasis progression of gallbladder cancer cells by regulating EMT-related pathways. Its expression level can be a novel biomarker for gallbladder cancer, providing new perspectives for diagnosis and treatment strategies.
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    Expression of EMT inducers integrin-linked kinase (ILK) and ZEB1 in phyllodes breast tumors is associated with aggressive phenotype
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2018) Akrida, Ioanna; Nikou, Sofia; Gyftopoulos, Konstantinos; Argentou, Marianna; Kounelis, Sofia; Zolota, Vassiliki; Bravou, Vasiliki; Papadaki, Helen
    Phyllodes tumors (PTs) of the breast constitute an uncommon group of mammary fibroepithelial lesions with ambiguous biologic behavior. Recent evidence suggests that epithelial mesenchymal transition (EMT), a driving force of cancer progression is implicated in PTs pathogenesis. Integrin-linked kinase (ILK), a focal adhesion kinase, has been implicated in cancer and EMT and represents a novel cancer therapeutic target. In this study, we aimed to investigate ILK and EMT markers expression in phyllodes breast tumors in relation to tumor grade. Expression of ILK and EMT markers E-cadherin, β-catenin, Ν-cadherin, vimentin, Snail, ZEB1 and Twist was evaluated by immunohistochemistry in paraffin-embedded tissue sections from 96 human phyllodes breast tumors (48 benign, 27 borderline, 21 malignant). Cytoplasmic and nuclear immunopositivity of ILK were observed in both the epithelial and the stromal component of phyllodes breast tumors and were significantly higher with increasing tumor grade. An EMT-related expression profile consisting of decreased membranous and increased nuclear/cytoplasmic immunoreactivity of Ecadherin and β-catenin and increased expression of Ncadherin, vimentin, Snail, ZEB1 and Twist was observed in tumor epithelial and stromal component and was significantly associated with malignant phyllodes breast tumor histopathology. Interestingly, there was a significant correlation of ILK expression with all of the EMT markers examined. Our results suggest that EMT significantly contributes to phyllodes tumor pathogenesis and originally implicate ILK and ZEB1 in phyllodes tumors malignant phenotype.
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    LncRNA ADAMTS9-AS1 knockdown restricts cell proliferation and EMT in non-small cell lung cancer
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2021) Li, Zhongwen; Yue, Guojun; Zhang, Tingyou; Wu, Jinzhi; Tian, Xin
    A recent bioinformatics analysis identified long non‐coding RNA antisense 1 ADAMTS9-AS1 as an independent prognostic marker in several tumors, including prostate cancer and bladder cancer. Nevertheless, the prognostic value and functional role of ADAMTS9-AS1 in non-small cell lung cancer (NSCLC) remain elusive. Here, we first found that the expression of ADAMTS9-AS1 was significantly upregulated in NSCLC tissues compared with adjacent normal tissues using quantitative real time PCR analysis. Clinically, we observed that ADAMTS9-AS1 expression was associated with TNM stage, lymph node metastasis and poor prognosis in NSCLC patients. By performing lossof-function assay in A549 and 95D cells, our in vitro experiments further showed that knockdown of ADAMTS9-AS1 remarkedly suppressed cell proliferation, caused cell cycle G0/G1 arrest and apoptosis, and inhibited cell migration and invasion in NSCLC cells using CCK-8, colony formation, flow cytometry and transwell assays. Moreover, we found that ADAMTS9-AS1 knockdown downregulated the expression of CDK4, N-cadherin, Vimentin, but upregulated the expression of Bad and E-cadherin. In summary, our results revealed that ADAMTS9-AS1 may serve as a potential therapeutic target for the treatment of patients with NSCLC
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    Protein atlas of fibroblast specific protein 1 (FSP1)/S100A4
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Fendt, Bettina Marturet; Hirschmann, Astrid; Bruns, Malgorzata; Camarillo Retamosa, Eva; Ospelt, Caroline; Vogetseder, Alexander
    Fibroblast specific protein 1 (FSP1)/S100A4 is a calcium binding protein which has been linked to epithelial-mesenchymal transition, tissue fibrosis, pulmonary vascular disease, metastatic tumour development, increased tumour cell motility and invasiveness. This protein is reported to be also expressed in newly formed and differentiated fibroblasts and has been used in various studies to demonstrate epithelial-mesenchymal transition (EMT). We aimed to characterize S100A4 positive cells in different human tissue compartments, with the focus on fibroblasts/myofibroblast. We found S100A4 expression in a wide range of cells. Fibroblasts/myofibroblasts showed a broad spectrum of staining intensity, ranging from negative to strong expression of S100A4, with the strongest expression in smooth muscle actin positive myofibroblasts. Cells of haematopoietic lineage, namely CD4 and CD8 positive T-lymphocytes, but not Blymphocytes expressed S100A4. All investigated monocytes, macrophages and specialised histiocytes were positive for S100A4. Even some epithelial cells of the kidney and bladder were positive for S100A4. Expression was also found in the vasculature. Here, cells of the subendothelial space, tunica adventitia and some smooth muscle cells of the tunica media were positive for S100A4. In summary, S100A4 is expressed in various cell types of different lineage and is not, as originally believed, specific for fibroblasts (FSP). Results attained under the premise of specificity of FSP1/S100A4 for fibroblasts, like the founding research on EMT type 2 in kidney and liver, therefore need to be reinterpreted.
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    The long non-coding RNA PANDAR regulates cell proliferation and epithelial-to-mesenchymal transition in glioma
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Guo, Jianfeng; Xiao, Deyong; Lin, Zhijing; Sui, Chengzhi
    Glioma is one of the most aggressive intracranial tumors in the central nervous system. The long non-coding RNA P21-associated ncRNA DNA damage activated (PANDAR) has been reported to be an oncogene or tumor suppressor in several cancers. However, the prognostic value and biological function of PANDAR in glioma have not been described. Here, we report that expression of PANDAR is significantly upregulated in glioma tissues and cell lines. PANDAR expression was correlated with tumor size (p=0.044) and World Health Organization (WHO) grades (p=0.005), as shown by chi-squared test. Moreover, significant upregulation of PANDAR was found to correlate with poor prognosis in glioma, as shown using Kaplan-Meier method and Cox multivariate survival analysis. Furthermore, PANDAR knockdown suppressed cell proliferation, G1/S transition, migration and invasion, and promoted apoptosis in glioma cell lines (U251 and U87). PANDAR knockdown decreased expression of CDK4, Bcl-2, N-cadherin and Vimentin, but increased E-cadherin expression in glioma cells. In conclusion, our data suggest PANDAR as a potential prognostic biomarker and therapeutic candidate for glioma.
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    The role of EpCAM in physiology and pathology of the epithelium
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2016) Martowicz, Agnieszka; Seeber, Andreas; Untergasser, Gerold
    Epithelial Cell Adhesion Molecule (EpCAM) has been discovered as one of the first tumor-specific antigens overexpressed in epithelial cancer. The present review focuses on the role of EpCAM in physiology and homeostasis of epithelia. Recent research pointed to a close interaction of EpCAM with other cell-cell contact molecules like E-cadherin and claudins and an intimate crosstalk with Wnt and TGF-beta signaling in the regulation of cell growth. Moreover, EpCAM has been shown to modulate trans-epithelial migration processes of white blood cells. Mutations of the EpCAM gene lead to disturbances of epithelial homeostasis and cellular differentiation from the stem cell compartment. In the intestinal tract EpCAM mutations contribute to congenital tufting enteropathy. Regarding tumorigenesis EpCAM can act as an oncogene still depending on additional driver mutations and epithelial phenotype of tumor cells. Tumor cells display increased EpCAM expression that often correlates with the loss of strict basolateral localization. Many tumors show enhanced regulated intramembrane proteolysis (RIP) of EpCAM and loose EpCAM expression under conditions of epithelial to mesenchymal transition. The resulting extracellular EpEX and intracellular EpICD fragments mediate proliferative signals to the cell. Resulting fragments can be validated either by sensitive enzymelinked immune-sandwich assays (EpEX) or by immunohistochemistry (EpICD). The present review gives an overview on the detection of EpCAM fragments as predictive markers for disease progression and survival of cancer patients.
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    Tripartite motif-containing 35 (TRIM35) is up-regulated in UUO-induced renal fibrosis animal model
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2020) Chen, Yu; Ding, Yue; Wang, Li-Ming
    Renal fibrosis has been recognized as a serious health threat in the world because of the high cost of treatment and poor prognosis. However, the molecular mechanism of renal fibrosis is still largely unknown. In this study, we aimed at illustrating the role of TRIM35 in the renal fibrosis process. A UUO mouse model and a TGF-β1-induced tubulointerstitial fibrosis model were constructed for the research of renal fibrosis at animal and cell level, respectively. Hematoxylin-eosin and Masson staining were used for visualizing the pathological change. qRT-PCR, Western blot analysis and immunohistochemical staining were used to detect the expression of fibrosis-associated proteins and TRIM35. The results showed that, after the modeling, the expressions of α-SMA, Collagen I, Collagen III, Fibronectin and Snail1 were up-regulated, while the expression of E-cadherin was down-regulated, indicating the successful construction of animal and cell models. More importantly, TRIM35 was proved to be upregulated in both animal and cell models. Therefore, this study demonstrates the potential promotional effect of TRIM35 in the renal fibrosis process, which may prove to be a new biomarker for the diagnosis and development of new treatments of renal fibrosis.