scholarly journals Isoliquiritigenin Reverses Epithelial-Mesenchymal Transition Through Modulation of the TGF-β/Smad Signaling Pathway in Endometrial Cancer

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1236
Author(s):  
Hsin-Yuan Chen ◽  
Yi-Fen Chiang ◽  
Jia-Syuan Huang ◽  
Tsui-Chin Huang ◽  
Yin-Hwa Shih ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Signaling Pathway ◽  
Cancer Cell ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Smad Signaling ◽  
Smad Signaling Pathway ◽  
E Cadherin

Endometrial cancer is a common gynecological cancer with a poor prognosis, mostly attributed to tumor metastasis. Epithelial–mesenchymal transition (EMT) can be mediated via transforming growth factor beta (TGF-β) signaling pathway, facilitating the ability of cancer cell invasion and migration. Isoliquiritigenin (ISL) is a flavonoid derived from licorice with reported antineoplastic activities. This study aims to investigate the anti-metastatic potential of ISL on endometrial cancer both in vitro and in vivo. First, human endometrial cancer cell lines (HEC-1A, Ishikawa, and RL95-2) were treated with ISL and then subjected to functional assays such as migration assay as well as molecular analyses including immunoblotting, immunofluorescence and RT-qPCR. In addition, HEC-1A-LUC cells were implanted into female nude mice and treated with ISL by intraperitoneal injection for four weeks. Results showed that ISL inhibited cell migration and reversed the effect of TGF-β on the expression of E-cadherin, N-cadherin, vimentin, α-SMA, p-Smad3, and TWIST1/2 In vitro. Interestingly, In vivo study revealed that ISL reduced peritoneal dissemination and serum level of TGF-β1, as well as decreased the expression levels of N-cadherin, p-Smad2/3, TWIST1/2, while increased E-cadherin. Overall, ISL reverses the EMT through targeting the TGF-β/Smad signaling pathway and features a potential therapeutic treatment for metastatic endometrial cancer.

scholarly journals The EIF4A3/CASC2/RORA Feedback Loop Regulates the Aggressive Phenotype in Glioblastomas

2021 ◽  
Vol 11 ◽  
Author(s):  
Junshuang Zhao ◽  
Yang Jiang ◽  
Lian Chen ◽  
Yue Ma ◽  
Haiying Zhang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Feedback Loop ◽  
Biological Effects ◽  
Gene Set Enrichment Analysis ◽  
Mesenchymal Transition ◽  
Smad Signaling ◽  
Smad Signaling Pathway ◽  
Tgf Β1

Glioblastoma (GBM) is a common and refractory subtype of high-grade glioma with a poor prognosis. The epithelial-mesenchymal transition (EMT) is an important cause of enhanced glioblastoma invasiveness and tumor recurrence. Our previous study found that retinoic acid receptor-related orphan receptor A (RORA) is a nuclear receptor and plays an important role in inhibiting proliferation and tumorigenesis of glioma. We further confirmed RORA was downregulated in GBM. Thus, we determined whether RORA was involved in the migration, invasion, and EMT of GBM. Human GBM cell lines, U87 and T98G, and patient-derived glioma stem cells (GSCs), GSC2C and GSC4D, were used for in vitro and in vivo experiments. The expressions of RORA, CASC2, and EIF4A3 in GBM cells and GSCs were detected by RT-qPCR and western blotting. The biological effects of RORA, CASC2, and EIF4A3 on GBM migration, invasion, and EMT were evaluated using the migration assay, transwell assay, immunofluorescence staining, and xenograft experiments. We found that RORA inhibited the migration, invasion, and EMT of GBM. CASC2 could bind to, maintain the stability, and promote the nuclear translocation of RORA protein. EIF4A3 could downregulate CASC2 expression via inducing its cleavage, while RORA transcriptionally inhibited EIF4A3 expression, which formed a feedback loop among EIF4A3/CASC2/RORA. Moreover, gene set enrichment analysis (GSEA) and in vitro and in vivo experiments showed RORA inhibited the aggressiveness of GBM by negatively regulating the TGF-β1/Smad signaling pathway. Therefore, The EIF4A3/CASC2/RORA feedback loop regulated TGF-β1/Smad signaling pathway might become a promising therapeutic strategy for GBM treatment.

scholarly journals Periplaneta Americana Extract may Attenuate 2,4,6-Trinitrobenzenesulfonic Acid-Induced Intestinal Fibrosis by Inhibiting TGF-β/Smad Signaling Pathway

2021 ◽  
Author(s):  
Jing Liu ◽  
Pin Lv ◽  
Xiang Rao ◽  
Jiajia Wang
Keyword(s):  
Western Blot ◽  
Signaling Pathway ◽  
Real Time Pcr ◽  
Periplaneta Americana ◽  
Collagen I ◽  
Smad Signaling ◽  
Intestinal Fibrosis ◽  
Smad Signaling Pathway

Abstract PurposeIntestinal fibrosis is an incurable digestive disease accompanied by stricture formation, and it has an increasing incidence in recent years. Periplaneta americana is one of the medicinal insects with a long history. There are few reports on the effect of intestinal fibrosis. This study aims to evaluate the inhibitory effect of PA treatment on intestinal fibrosis. MethodsTNBS was used to establish intestinal fibrosis model by enema in BALB/c mice. The mice were treated with PA (50, 100, 200 mg/kg body weight) and 5-aminosalicylic acid (5-ASA) (40mg/kg) by gavage once a day for 6 weeks. At the end of the last week, the mice were sacrificed. Colon samples were collected for H&E and Masson staining. The mRNA and protein expression of α-smooth muscle actin (α-SMA), collagen I and the transforming growth factor-β (TGF-β) / Smad signaling pathway were conducted by real-time PCR and western blot analysis. In vitro, TGF-β1 was used to induce intestinal fibrosis at human colon fibroblasts (CCD-18Co). And using real-time PCR and western blot methods to detect the expression of α-SMA and collagen I. ResultsPA inhibited the expression of α-SMA and collagen I in vivo and in vitro. But the difference was that PA inhibited the TGF-β/Smad signaling pathway in vivo, and the same results had not been obtained in vitro. Conclusion: PA may attenuate intestinal fibrosis by inhibiting TGF-β/Smad signaling pathway, but more experiments were needed to prove it in vitro. ConclusionsPA has potential pharmacological effects in inhibiting intestinal fibrosis, and the TGF-β/Smad signaling pathway seemed promising.

scholarly journals Bone morphogenetic protein-7 prevented epithelial-mesenchymal transition in RLE-6TN cells

2016 ◽  
Vol 5 (3) ◽  
pp. 931-937 ◽  
Author(s):  
Yan Wang ◽  
Di Liang ◽  
Zhonghui Zhu ◽  
Xiaoli Li ◽  
Guoliang An ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Bone Morphogenetic Protein ◽  
Signaling Pathway ◽  
P38 Mapk ◽  
Epithelial Mesenchymal Transition ◽  
Bone Morphogenetic Protein 7 ◽  
Mesenchymal Transition ◽  
Morphogenetic Protein

Silica induced EMT and decreased the expression of BMP-7 in vivo and in vitro, while exogenous BMP-7 promoted MET and inhibited silica-induced EMT associated with inhibition of the p38 MAPK/transcription factor (TF) signaling pathway in RLE-6TN cells.

scholarly journals Tangzhiqing Granules Alleviate Podocyte Epithelial-Mesenchymal Transition in Kidney of Diabetic Rats

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Haiyan Xu ◽  
Xu Wang ◽  
Mingming Liu ◽  
Xueyuan He
Keyword(s):  
Molecular Markers ◽  
Treatment Group ◽  
Signaling Pathway ◽  
Epithelial Mesenchymal Transition ◽  
Diabetic Rats ◽  
High Dose ◽  
Mesenchymal Transition ◽  
Dose Treatment ◽  
Smad Signaling ◽  
Smad Signaling Pathway

This study discussed the effect of Tangzhiqing granules on podocyte epithelial-mesenchymal transition in kidney of diabetic rats. The diabetic rats were divided randomly into five groups: DM group treated with vehicle, Tangzhiqing granules low-dose treatment group, Tangzhiqing granules middle-dose treatment group, and Tangzhiqing granules high-dose treatment group. Eight Wistar rats used as control group were given saline solution. The intervention was all intragastric administration for 8 weeks. At the end of the 8 weeks, biochemical parameters and kidney weight/body weight ratio were measured. The kidney tissues were observed under light microscope and transmission electron microscopy. To search for the underlying mechanism, we examined the epithelial-to-mesenchymal transition (EMT) related molecular markers and TGF-β/smad signaling pathway key proteins expression. The results showed that Tangzhiqing granules relieved the structural damage and functional changes of diabetic kidneys. Kidney podocyte EMT related molecular markers nephrin and CD2AP expression were increased, when desmin and α-SMA levels were decreased by Tangzhiqing granules in diabetic rats. Further TGF-β/smad signaling pathway key proteins TGF-β1 and p-smad2/3 levels were decreased in diabetic rats after treatment with Tangzhiqing granules. These findings suggest that Tangzhiqing granules may protect the podocytes of diabetic nephropathy rats via alleviating podocyte EMT and likely activating TGFβ/smad signaling pathway.

scholarly journals SMARCC1 Suppresses Tumor Progression by Inhibiting the PI3K/AKT Signaling Pathway in Prostate Cancer

2021 ◽  
Vol 9 ◽  
Author(s):  
Zhao-Ming Xiao ◽  
Dao-Jun Lv ◽  
Yu-zhong Yu ◽  
Chong Wang ◽  
Tao Xie ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Proliferation ◽  
Signaling Pathway ◽  
Cell Cycle Progression ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Proliferation And Metastasis ◽  
Cell Proliferation And Metastasis

BackgroundSWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin subfamily C member 1 (SMARCC1) protein is a potential tumor suppressor in various cancers. However, its role in prostate cancer (PCa) remains controversial. The aim of this study was to determine the biological function of SMARCC1 in PCa and explore the underlying regulatory mechanisms.MethodsThe expression of SMARCC1 was validated in PCa tissues by immunohistochemistry. Meanwhile, function experiments were used to evaluate the regulatory role on cell proliferation and metastasis in PCa cells with SMARCC1 depletion both in vitro and in vivo. The expression levels of relevant proteins were detected by Western blotting.ResultsOur finding showed that SMARCC1 was significantly downregulated in prostate adenocarcinoma, with a higher Gleason score (GS) than that in low GS. The decreased expression of SMARCC1 was significantly correlated with a higher GS and poor prognosis. Additionally, we found that silencing of SMARCC1 dramatically accelerated cell proliferation by promoting cell cycle progression and enhancing cell migration by inducing epithelial mesenchymal transition (EMT). Furthermore, depletion of SMARCC1 facilitated PCa xenograft growth and lung metastasis in murine models. Mechanistically, the loss of SMARCC1 activated the PI3K/AKT pathway in PCa cells.ConclusionSMARCC1 suppresses PCa cell proliferation and metastasis via the PI3K/AKT signaling pathway and is a novel therapeutic target.

scholarly journals DcR3 induces epithelial-mesenchymal transition through activation of the TGF-β3/SMAD signaling pathway in CRC

Oncotarget ◽  
2016 ◽  
Vol 7 (47) ◽  
pp. 77306-77318 ◽  
Author(s):  
Yan-Ping Liu ◽  
Hui-Fang Zhu ◽  
Ding-li Liu ◽  
Zhi-Yan Hu ◽  
Sheng-Nan Li ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Smad Signaling ◽  
Smad Signaling Pathway

scholarly journals Arctigenin Suppressed Epithelial-Mesenchymal Transition Through Wnt3a/β-Catenin Pathway in PQ-Induced Pulmonary Fibrosis

2020 ◽  
Vol 11 ◽  
Author(s):  
Fei Gao ◽  
Yun Zhang ◽  
Zhizhou Yang ◽  
Mengmeng Wang ◽  
Zhiyi Zhou ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Signaling Pathway ◽  
Lung Fibrosis ◽  
Epithelial Mesenchymal Transition ◽  
A549 Cells ◽  
Underlying Mechanism ◽  
Alveolar Type ◽  
Mesenchymal Transition

Arctigenin (ATG), a major bioactive substance of Fructus Arctii, counters renal fibrosis; however, whether it protects against paraquat (PQ)-induced lung fibrosis remains unknown. The present study was to determine the effect of ATG on PQ-induced lung fibrosis in a mouse model and the underlying mechanism. Firstly, we found that ATG suppressed PQ-induced pulmonary fibrosis by blocking the epithelial-mesenchymal transition (EMT). ATG reduced the expressions of Vimentin and α-SMA (lung fibrosis markers) induced by PQ and restored the expressions of E-cadherin and Occludin (two epithelial markers) in vivo and in vitro. Besides, the Wnt3a/β-catenin signaling pathway was significantly activated in PQ induced pulmonary fibrosis. Further analysis showed that pretreatment of ATG profoundly abrogated PQ-induced EMT-like phenotypes and behaviors in A549 cells. The Wnt3a/β-catenin signaling pathway was repressed by ATG treatment. The overexpression of Wnt3a could weaken the therapeutic effect of ATG in A549 cells. These findings suggested that ATG could serve as a new therapeutic candidate to inhibit or even reverse EMT-like changes in alveolar type II cells during PQ-induced lung fibrosis, and unraveled that the Wnt3a/β-catenin pathway might be a mechanistic tool for ATG to control pulmonary fibrosis.

ZBTB7A promotes migration, invasion and metastasis of human breast cancer cells through NF-κB-induced epithelial–mesenchymal transition in vitro and in vivo

2019 ◽  
Vol 166 (6) ◽  
pp. 485-493 ◽  
Author(s):  
Anyun Mao ◽  
Maojian Chen ◽  
Qinghong Qin ◽  
Zhijie Liang ◽  
Wei Jiang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Epithelial Mesenchymal Transition ◽  
Migration And Invasion ◽  
Cancer Tissue ◽  
Mesenchymal Transition ◽  
Mcf 7

Abstract It has been generally confirmed that zinc finger and BTB domain containing 7A (ZBTB7A) plays an important role in the occurrence and progression of malignant tumours, but the promotion or inhibition effect is related to tumour type. The mechanism between ZBTB7A and breast cancer is not well understood, so further research is needed. In this study, we first investigated the expression of ZBTB7A in tissue samples of clinical breast cancer patients, MDA-MB-231, MCF-7 and MCF-10A cells. Second, we overexpressed the ZBTB7A in MCF-7 cells and silenced the ZBTB7A in MDA-MB-231 cells using lentivirus transfection technology, respectively, and verified the effect of ZBTB7A on migration and invasion of breast cancer cell lines through in vitro cell function experiments, such as wound-healing assay, migration and invasion assay, quantitative real time reverse transcriptase (qRT-PCR) and western blot. Then, the correlation between the above influences, epithelial–mesenchymal transition (EMT) and NF-κB was analysed. Finally, in vivo tumour transplantation model in nude mice was established to verified the effect of ZBTB7A on metastasis of breast cancer MDA-MB-231 cells. In conclusion, ZBTB7A is highly expressed in cancer tissue, breast cancer cell line MDA-MB-231 and MCF-7. Meanwhile, the high expression of ZBTB7A may promote cell migration, invasion and tumour metastasis, which may be related to EMT events by regulating NF-κB.

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