Sa1787 Regulation of Chemotherapy Resistance Through Epithelial-Mesenchymal Transition by Zinc Finger E-Box-Binding Proteins

2012 ◽  
Vol 142 (5) ◽  
pp. S-326
Author(s):  
Shinya Ohashi ◽  
Seiji Naganuma ◽  
Mitsuteru Natsuizaka ◽  
Shingo Kagawa ◽  
Hideaki Kinugasa ◽  
...  
Keyword(s):  
Zinc Finger ◽  
Binding Proteins ◽  
Epithelial Mesenchymal Transition ◽  
Chemotherapy Resistance ◽  
Mesenchymal Transition ◽  
E Box

scholarly journals Plasmacytoid urothelial carcinoma of renal pelvis with positive zinc finger E–box–binding homeobox 1: a case report

2020 ◽  
Author(s):  
Atsuko Takada-Owada ◽  
Yumi Nozawa ◽  
Masato Onozaki ◽  
Shuhei Noda ◽  
Tsengelumaa Jamiyan ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Zinc Finger ◽  
Renal Pelvis ◽  
Plasma Cells ◽  
Epithelial Mesenchymal Transition ◽  
Resected Specimen ◽  
Mesenchymal Transition ◽  
E Box ◽  
Tumor Transformation ◽  
E Cadherin

Abstract BackgroundThe tumor transformation mechanism of a plasmacytoid urothelial carcinoma remains unexplained. We describe the case of a plasmacytoid urothelial carcinoma of the renal pelvis in which the expression of zinc finger E–box–binding homeobox 1 (ZEB1), a key nuclear transcription factor in an epithelial–mesenchymal transition, is involved in tumor transformation.Case presentationThe patient had a left nephrectomy with the clinical diagnosis of left pelvic renal cancer. The resected specimen showed that the tumor surface comprised a noninvasive papillary urothelial carcinoma with the carcinoma in situ, and the invasive area comprised a plasmacytoid urothelial carcinoma characterized by the presence of single dyscohesive malignant cells that resembled plasma cells in a loose myxoid stroma. The noninvasive urothelial carcinoma was positive for cytokeratin and E–cadherin, and negative for vimentin and ZEB1. In contrast, the invasive plasmacytoid urothelial carcinoma was positive for cytokeratin and also vimentin and ZEB1, and negative for E–cadherin. Additionally, this component was immunoreactive for CD138 and CD38 that are immunohistochemical markers for plasma cells.ConclusionWe suggest that ZEB1 is involved in the plasmacytoid transformation by repressing the E–cadherin in a plasmacytoid urothelial carcinoma.

scholarly journals Plasmacytoid urothelial carcinoma of renal pelvis with positive zinc finger E–box–binding homeobox 1: a case report

2020 ◽  
Author(s):  
Atsuko Takada-Owada ◽  
Yumi Nozawa ◽  
Masato Onozaki ◽  
Shuhei Noda ◽  
Tsengelumaa Jamiyan ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Zinc Finger ◽  
Renal Pelvis ◽  
Plasma Cells ◽  
Epithelial Mesenchymal Transition ◽  
Resected Specimen ◽  
Mesenchymal Transition ◽  
E Box ◽  
Tumor Transformation ◽  
E Cadherin

Abstract BackgroundThe tumor transformation mechanism of a plasmacytoid urothelial carcinoma remains unexplained. We describe the case of a plasmacytoid urothelial carcinoma of the renal pelvis in which the expression of zinc finger E–box–binding homeobox 1 (ZEB1), a key nuclear transcription factor in an epithelial–mesenchymal transition, is involved in tumor transformation.Case presentationThe patient had a left nephrectomy with the clinical diagnosis of left pelvic renal cancer. The resected specimen showed that the tumor surface comprised a noninvasive papillary urothelial carcinoma with the carcinoma in situ, and the invasive area comprised a plasmacytoid urothelial carcinoma characterized by the presence of single dyscohesive malignant cells that resembled plasma cells in a loose myxoid stroma. The noninvasive urothelial carcinoma was positive for cytokeratin and E–cadherin, and negative for vimentin and ZEB1. In contrast, the invasive plasmacytoid urothelial carcinoma was positive for cytokeratin and also vimentin and ZEB1, and negative for E–cadherin. Additionally, this component was immunoreactive for CD138 and CD38 that are immunohistochemical markers for plasma cells.ConclusionWe suggest that ZEB1 is involved in the plasmacytoid transformation by repressing the E–cadherin in a plasmacytoid urothelial carcinoma.

Zinc finger E-box-binding homeobox 1 (ZEB1): A novel predictor for the prognosis in gastrointestinal tumors.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e23515-e23515
Author(s):  
Shenglan Yang ◽  
Jiang Min
Keyword(s):  
Zinc Finger ◽  
Epithelial Mesenchymal Transition ◽  
High Expression ◽  
Mesenchymal Transition ◽  
Cancer Breast ◽  
Female Rate ◽  
Significant Difference ◽  
E Box ◽  
Progression Of Disease ◽  
Low Expression

e23515 Background: The gastrointestinal stromal tumors (GISTs) are the most common soft tissue sarcoma arising anywhere along gastrointestinal tract. The advanced and metastatic GISTs are the leading cause in GISTs inducing death. GISTs are the most commonly resulted from KIT or PDGFRA activation mutation. Currently adjuvant therapy with imatinib also targets the KIT and PDGFRA signals, which significantly increases the relapse-free survival and overall survival. However, KIT and PDGFRA mutation are not completely responsible for the progression of disease, especially metastasis of GISTs. So, there could be other molecular mechanism in GISTs progression. ZEB1 (zinc finger E-box-binding homeobox 1), as a member in zinc finger and homeodomain transcriptional factor family, plays a key role in metastasis of some epithelial carcinomas, such as colorectal cancer, breast cancer and NSCLC. We present that ZEB1, as a vital molecular in epithelial-mesenchymal transition, could be a promising marker in predicting the prognosis in GISTs. Methods: Immunohistochemistry staining for paraffin-embedding slices from 157 patients firstly diagnosed as GIST is applied for detecting the ZEB1 expression. Clinical, pathological, molecular and survival time were analyzed. All performances were approved by the Medical Ethics Committee in the First Affiliated Hospital of Chongqing Medical University. Results: In 157 patients, metastasis was found in 87 patients. In 87 patients with metastasis, high expression of ZEB1 almost exhibited (80 high/96 VS 7 non or low/96), while non or low expression was frequently detected in patients without metastasis (50 non or low/70 VS 20 high/70) (p < 0.0001). There was no significant difference between high and non/low expression patients in gender (48% VS 46% for male rate; 52% VS 54% for female rate), age (53 vs 54 years for median age), primary location (esophagus 2% VS 1.8%; stomach 57% VS 52.6%; duodenum and small intestine 31% VS 31.6%; colorectum and anus 10% VS 14.0%), tumor size (0.5-24cm, median 9.7cm VS 1-25.5cm, median 10.1cm), mitotic index (55.0% VS 58.6% for > 5/50HPF; 45.0% VS 41.4% for ≤5/50HPF), and risk stratification (low/intermediate risk 60.7% VS 63%; high risk 39.3% VS 37%). In addition, the 5-year OS rate was considerably lower in patients with ZEB1 high expression than those with ZEB1 none or low expression at baseline (37% vs 86%; p = 0.011). Conclusions: High expression of ZEB1 facilitates metastasis and indicates the poor prognosis in GISTs. ZEB1 could be a novel predictor for GIST’s prognosis.

scholarly journals Plasmacytoid urothelial carcinoma of renal pelvis with positive zinc finger E–box–binding homeobox 1: a case report

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Atsuko Takada-Owada ◽  
Yumi Nozawa ◽  
Masato Onozaki ◽  
Shuhei Noda ◽  
Tsengelmaa Jamiyan ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Zinc Finger ◽  
Renal Pelvis ◽  
Plasma Cells ◽  
Epithelial Mesenchymal Transition ◽  
Resected Specimen ◽  
Mesenchymal Transition ◽  
E Box ◽  
Tumor Transformation ◽  
E Cadherin

Abstract Background The tumor transformation mechanism of a plasmacytoid urothelial carcinoma remains unexplained. We describe the case of a plasmacytoid urothelial carcinoma of the renal pelvis in which the expression of zinc finger E–box–binding homeobox 1 (ZEB1), a key nuclear transcription factor in an epithelial–mesenchymal transition, is involved in tumor transformation. Case presentation The patient had a left nephrectomy with the clinical diagnosis of left pelvic renal cancer. The resected specimen showed that the tumor surface comprised a noninvasive papillary urothelial carcinoma with the carcinoma in situ, and the invasive area comprised a plasmacytoid urothelial carcinoma characterized by the presence of single dyscohesive malignant cells that resembled plasma cells in a loose myxoid stroma. The noninvasive urothelial carcinoma was positive for cytokeratin and E–cadherin, and negative for vimentin and ZEB1. In contrast, the invasive plasmacytoid urothelial carcinoma was positive for cytokeratin and also vimentin and ZEB1, and negative for E–cadherin. Additionally, this component was immunoreactive for CD138 and CD38 that are immunohistochemical markers for plasma cells. Conclusion We suggest that ZEB1 is involved in the plasmacytoid transformation by repressing the E–cadherin in a plasmacytoid urothelial carcinoma.

scholarly journals Form follows function: Morphological and immunohistological insights into epithelial–mesenchymal transition characteristics of tumor buds

Tumor Biology ◽  
2017 ◽  
Vol 39 (5) ◽  
pp. 101042831770550 ◽  
Author(s):  
Kathrin Enderle-Ammour ◽  
Moritz Bader ◽  
Theresa Dorothee Ahrens ◽  
Kai Franke ◽  
Sylvia Timme ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Zinc Finger ◽  
Cell Morphology ◽  
Epithelial Mesenchymal Transition ◽  
Three Dimensional ◽  
Tumor Budding ◽  
Mesenchymal Transition ◽  
Tumor Mass ◽  
E Box ◽  
E Cadherin

In cancer biology, the architectural concept “form follows function” is reflected by cell morphology, migration, and epithelial–mesenchymal transition protein pattern. In vivo, features of epithelial–mesenchymal transition have been associated with tumor budding, which correlates significantly with patient outcome. Hereby, the majority of tumor buds are not truly detached but still connected to a major tumor mass. For detailed insights into the different tumor bud types and the process of tumor budding, we quantified tumor cells according to histomorphological and immunohistological epithelial–mesenchymal transition characteristics. Three-dimensional reconstruction from adenocarcinomas (pancreatic, colorectal, lung, and ductal breast cancers) was performed as published. Tumor cell morphology and epithelial–mesenchymal transition characteristics (represented by zinc finger E-box-binding homeobox 1 and E-Cadherin) were analyzed qualitatively and quantitatively in a three-dimensional context. Tumor buds were classified into main tumor mass, connected tumor bud, and isolated tumor bud. Cell morphology and epithelial–mesenchymal transition marker expression were assessed for each tumor cell. Epithelial–mesenchymal transition characteristics between isolated tumor bud and connected tumor bud demonstrated no significant differences or trends. Tumor cell count correlated significantly with epithelial–mesenchymal transition and histomorphological characteristics. Regression curve analysis revealed initially a loss of membranous E-Cadherin, followed by expression of cytoplasmic E-Cadherin and subsequent expression of nuclear zinc finger E-box-binding homeobox 1. Morphologic changes followed later in this sequence. Our data demonstrate that connected and isolated tumor buds are equal concerning immunohistochemical epithelial–mesenchymal transition characteristics and histomorphology. Our data also give an insight in the process of tumor budding. While there is a notion that the epithelial–mesenchymal transition zinc finger E-box-binding homeobox 1–E-Cadherin cascade is initiated by zinc finger E-box-binding homeobox 1, our results are contrary and outline other possible pathways influencing the regulation of E-Cadherin.

scholarly journals A novel homeostatic loop of sorcin drives paclitaxel-resistance and malignant progression via Smad4/ZEB1/miR-142-5p in human ovarian cancer

Oncogene ◽  
2021 ◽  
Author(s):  
Jinguo Zhang ◽  
Wencai Guan ◽  
Xiaolin Xu ◽  
Fanchen Wang ◽  
Xin Li ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Calcium Binding ◽  
Molecular Mechanisms ◽  
Epithelial Mesenchymal Transition ◽  
Malignant Progression ◽  
Bioinformatics Analyses ◽  
Aberrant Expression ◽  
Mesenchymal Transition ◽  
E Box

AbstractThe primary chemotherapy of ovarian cancer (OC) often acquires chemoresistance. Sorcin (SRI), a soluble resistance-related calcium-binding protein, has been reported to be an oncogenic protein in cancer. However, the molecular mechanisms of SRI regulation and the role and aberrant expression of SRI in chemoresistant OC remain unclear. Here, we identified SRI as a key driver of paclitaxel (PTX)-resistance and explored its regulatory mechanism. Using transcriptome profiles, qRT-PCR, proteomics, Western blot, immunohistochemistry, and bioinformatics analyses, we found that SRI was overexpressed in PTX-resistant OC cells and the overexpression of SRI was related to the poor prognosis of patients. SRI was a key molecule required for growth, migration, and PTX-resistance in vitro and in vivo and was involved in epithelial–mesenchymal transition (EMT) and stemness. Mechanistic studies showed that miR-142-5p directly bound to the 3ʹ-UTR of SRI to suppress its expression, whereas a transcription factor zinc-finger E-box binding homeobox 1 (ZEB1) inhibited the transcription of miR-142-5p by directly binding to the E-box fragment in the miR-142 promoter region. Furthermore, ZEB1 was negatively regulated by SRI which physically interacted with Smad4 to block its translocation from the cytosol to the nucleus. Taken together, our findings unveil a novel homeostatic loop of SRI that drives the PTX-resistance and malignant progression via Smad4/ZEB1/miR-142-5p in human OC. Targeting this SRI/Smad4/ZEB1/miR-142-5p loop may reverse the PTX-resistance.

scholarly journals CD90low glioma-associated mesenchymal stromal/stem cells promote temozolomide resistance by activating FOXS1-mediated epithelial-mesenchymal transition in glioma cells

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Bing-zhou Xue ◽  
Wei Xiang ◽  
Qing Zhang ◽  
Hao-fei Wang ◽  
Yu-jie Zhou ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Line ◽  
Epithelial Mesenchymal Transition ◽  
Chemotherapy Resistance ◽  
Glioma Cells ◽  
Conditioned Media ◽  
Cell Counting ◽  
Mesenchymal Transition ◽  
Mesenchymal Transformation ◽  
Stromal Stem Cells

Abstract Background The tumour microenvironment contributes to chemotherapy resistance in gliomas, and glioma-associated mesenchymal stromal/stem cells (gaMSCs) are important stromal cell components that play multiple roles in tumour progression. However, whether gaMSCs affect chemotherapy resistance to the first-line agent temozolomide (TMZ) remains unclear. Herein, we explored the effect and mechanism of gaMSCs on resistance to TMZ in glioma cells. Methods Human glioma cells (cell line U87MG and primary glioblastoma cell line GBM-1) were cultured in conditioned media of gaMSCs and further treated with TMZ. The proliferation, apoptosis and migration of glioma cells were detected by Cell Counting Kit-8 (CCK-8), flow cytometry and wound-healing assays. The expression of FOXS1 in glioma cells was analysed by gene microarray, PCR and Western blotting. Then, FOXS1 expression in glioma cells was up- and downregulated by lentivirus transfection, and markers of the epithelial-mesenchymal transformation (EMT) process were detected. Tumour-bearing nude mice were established with different glioma cells and treated with TMZ to measure tumour size, survival time and Ki-67 expression. Finally, the expression of IL-6 in gaMSC subpopulations and its effects on FOXS1 expression in glioma cells were also investigated. Results Conditioned media of gaMSCs promoted the proliferation, migration and chemotherapy resistance of glioma cells. The increased expression of FOXS1 and activation of the EMT process in glioma cells under gaMSC-conditioned media were detected. The relationship of FOXS1, EMT and chemotherapy resistance in glioma cells was demonstrated through the regulation of FOXS1 expression in vitro and in vivo. Moreover, FOXS1 expression in glioma cells was increased by secretion of IL-6 mainly from the CD90low gaMSC subpopulation. Conclusions CD90low gaMSCs could increase FOXS1 expression in glioma cells by IL-6 secretion, thereby activating epithelial-mesenchymal transition and resistance to TMZ in glioma cells. These results indicate a new role of gaMSCs in chemotherapy resistance and provide novel therapeutic targets.

scholarly journals lncCRLA enhanced chemoresistance in lung adenocarcinoma that underwent epithelial-mesenchymal transition

2021 ◽  
Author(s):  
Weili Min ◽  
Liangzhang Sun ◽  
Burong Li ◽  
Xiao Gao ◽  
Shuqun Zhang ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Epithelial Mesenchymal Transition ◽  
Chemotherapy Resistance ◽  
Metastatic Potential ◽  
Caspase 8 ◽  
Mesenchymal Transition ◽  
Adenocarcinoma Cells ◽  
Signaling Axis ◽  
Lung Adenocarcinoma Cells ◽  
Paclitaxel Liposome

EMT confers increased metastatic potential and the resistance to chemotherapies to cancer cells. However, the precise mechanisms of EMT-related chemotherapy resistance remain unclear. c-Src-mediated Caspase-8 phosphorylation essential for EMT in lung adenocarcinoma cell lines preferentially occurs in cells with the mesenchymal phenotype, resulting in chemoresistance to cisplatin plus paclitaxel inpatients with resectable lung adenocarcinoma and a significantly worse 5-year PFS. Cisplatin killed lung adenocarcinoma cells regardless of Caspase-8. Paclitaxel-triggered necroptosis in lung adenocarcinoma cells was dependent on the phosphorylation or deficiency of Caspase-8, during which FADD interacted with RIPK1 to activateRIPK1/RIPK3/MLKL signaling axis. Accompanied with c-Src-mediated Caspase-8 phosphorylation to trigger EMT, a novel lncRNA named lncCRLA was markedly upregulated and inhibited RIPK1-induced necroptosis by impairing RIPK1-RIPK3 interaction via binding to the intermediate domain of RIPK1. Dasatinib mitigated c-Src-mediated phosphorylation of Caspase-8-induced EMT and enhanced necroptosis in mesenchymal-like lung adenocarcinoma cells treated with paclitaxel, while c-FLIP knockdown predominantly sensitized the mesenchymal-like lung adenocarcinoma cells to paclitaxel+dasatinib. c-Src-Caspase-8 interaction initiates EMT and chemoresistance viaCaspase-8 phosphorylation and lncCRLA expression, to which the dasatinib/paclitaxel liposome+siFLIP regimen was lethal.

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