scholarly journals SOX4 is associated with poor prognosis in prostate cancer and promotes epithelial–mesenchymal transition in vitro

2013 ◽  
Vol 16 (4) ◽  
pp. 301-307 ◽  
Author(s):  
L Wang ◽  
J Zhang ◽  
X Yang ◽  
Y W Y Chang ◽  
M Qi ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Poor Prognosis ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition

scholarly journals MicroRNA-144 Suppresses Prostate Cancer Growth and Metastasis by Targeting EZH2

2021 ◽  
Vol 20 ◽  
pp. 153303382198981
Author(s):  
Xin-bo Sun ◽  
Yong-wei Chen ◽  
Qi-sheng Yao ◽  
Xu-hua Chen ◽  
Min He ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Viability ◽  
Cell Apoptosis ◽  
Epithelial Mesenchymal Transition ◽  
Luciferase Reporter ◽  
Mesenchymal Transition ◽  
Proliferation And Apoptosis ◽  
High Incidence ◽  
Inhibit Cell Proliferation

Background: Prostate cancer is a common malignant tumor with a high incidence. MicroRNAs (miRNAs) have been shown to be important post-transcriptional regulators during tumorigenesis. This study aimed to explore the effect of miR-144 on PCa proliferation and apoptosis. Material and Methods: The expression of miR-144 and EZH2 were examined in clinical PCa tissues. PCa cell line LNCAP and DU-145 was employed and transfected with miR-144 mimics or inhibitors. The correlation between miR-144 and EZH2 was verified by luciferase reporter assay. Cell viability, apoptosis and migratory capacity were detected by CCK-8, flow cytometry assay and wound healing assay. The protein level of EZH2, E-Cadherin, N-Cadherin and vimentin were analyzed by western blotting. Results: miR-144 was found to be negatively correlated to the expression of EZH2 in PCa tissues. Further studies identified EZH2 as a direct target of miR-144. Moreover, overexpression of miR-144 downregulated expression of EZH2, reduced cell viability and promoted cell apoptosis, while knockdown of miR-144 led to an inverse result. miR-144 also suppressed epithelial-mesenchymal transition level of PCa cells. Conclusion: Our study indicated that miR-144 negatively regulate the expression of EZH2 in clinical specimens and in vitro. miR-144 can inhibit cell proliferation and induce cell apoptosis in PCa cells. Therefore, miR-144 has the potential to be used as a biomarker for predicting the progression of PCa.

scholarly journals Scorpion inhibits epithelial–mesenchymal transition and metastasis of hepatocellular carcinoma

2018 ◽  
Vol 243 (7) ◽  
pp. 645-654 ◽  
Author(s):  
Yi-Quan Yan ◽  
Juan Xie ◽  
Jing-Fu Wang ◽  
Zhao-Feng Shi ◽  
Xiang Zhang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Poor Prognosis ◽  
Epithelial Mesenchymal Transition ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Unfavorable Clinical Outcome ◽  
Metastasis Models ◽  
Tumor Growth And Metastasis

Hepatocellular carcinoma (HCC) is one of the most malignant diseases worldwide. The unfavorable clinical outcome and poor prognosis are due to high rates of recurrence and metastasis after treatments. Some scholars of traditional Chinese medicine suggested that endogenous wind-evil had played an important role in metastasis of malignant tumor. Therefore, the drug of dispelling wind-evil could be used to prevent cancer metastasis and improve the poor prognosis. So we wondered whether Scorpion, one of the most important wind calming drugs, has antitumor effect especially in epithelial–mesenchymal transition (EMT) and metastasis of HCC in this research. We found that Scorpion-medicated serum could inhibit proliferation, induce apoptosis, and decrease migration and invasion capacity of Hepa1-6 cells in vitro. Meanwhile, we observed that water decoction of Scorpion restrained tumor growth and metastasis in nude mouse of HCC metastasis models. Further experiments showed that Scorpion could suppress EMT, which is characterized by increased epithelial marker E-cadherin expression and decreased mesenchymal markers N-cadherin and Snail expression following Scorpion treatment both in vitro and in vivo. These results suggested that the Scorpion could inhibit Hepa1-6 cells’ invasion and metastasis in part by reversing EMT and providing a possible potential approach for preventing HCC metastasis. Impact statement The unfavorable clinical outcome and poor prognosis of hepatocellular carcinoma (HCC) are due to high rates of recurrence and metastasis after treatments. Here we found Scorpion, one of the most important wind calming drugs, has antitumor effect. Scorpion-medicated serum inhibited the proliferation, induced apoptosis, and decreased migration and invasion capacity of Hepa1-6 cells in vitro. Water decoction of Scorpion restrained tumor growth and metastasis in nude mouse of HCC metastasis models. Further experiments showed that Scorpion could suppress EMT of HCC both in vitro and in vivo. Our results suggested that the Scorpion could inhibit Hepa1-6 cells’ invasion and metastasis in part by reversing EMT and providing a possible potential approach for preventing HCC metastasis.

scholarly journals N-cadherin increases after androgen deprivation and is associated with metastasis in prostate cancer

2010 ◽  
Vol 17 (2) ◽  
pp. 469-479 ◽  
Author(s):  
Karin Jennbacken ◽  
Tajana Tešan ◽  
Wanzhong Wang ◽  
Heléne Gustavsson ◽  
Jan-Erik Damber ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Neuroendocrine Differentiation ◽  
Hormonal Treatment ◽  
Androgen Deprivation ◽  
Prostate Tumors ◽  
Primary Tumors ◽  
Mesenchymal Transition ◽  
Molecular Alterations

Androgen-deprivation therapy (ADT) is the standard treatment for metastatic prostate cancer. One factor that has been implicated in the metastatic process is the cell adhesion molecule N-cadherin. In this study, we investigated if the expression of N-cadherin was influenced by androgen deprivation and was associated with metastasis in prostate cancer. The effect of androgen deprivation on N-cadherin expression was initially studied in androgen-dependent (AD) LNCaP and androgen-independent (AI) LNCaP-19 and PC-3 prostate cancer cell lines. Expression of N-cadherin increased in the absence of androgens in AI LNCaP-19 primary tumors and metastases and also in vitro, but not in AI PC-3 tumors, indicating a possible involvement of the androgen receptor in the regulation of N-cadherin. N-cadherin was absent in AD LNCaP tumors. No clear associations between N-cadherin and factors related with epithelial–mesenchymal transition or neuroendocrine differentiation could be established. In addition, N-cadherin was evaluated by immunohistochemistry in human prostate tumors. Expression of N-cadherin was more frequently found in tumors from patients treated with ADT than in tumors from patients with no prior hormonal treatment. N-cadherin expression was also associated with metastasis and Gleason score. Furthermore, increased N-cadherin was detected in prostate cancer biopsies already 3 months after initiation of ADT when tumors were in a regressed state. In summary the results indicate that androgen deprivation induces N-cadherin in prostate tumors. Moreover, N-cadherin was increased in castration-resistant tumors in patients with established metastases. This might indicate that castration induces molecular alterations in the tumor cells, resulting in a more invasive and metastatic phenotype.

Wogonoside Inhibits Prostate Cancer Cell Growth and Metastasis via Regulating Wnt/β-Catenin Pathway and Epithelial-Mesenchymal Transition

Pharmacology ◽  
2019 ◽  
Vol 104 (5-6) ◽  
pp. 312-319 ◽  
Author(s):  
Can Wei ◽  
Junfeng Jing ◽  
Yanbin Zhang ◽  
Ling Fang
Keyword(s):  
Prostate Cancer ◽  
Cell Viability ◽  
Epithelial Mesenchymal Transition ◽  
Phase Cell ◽  
Dependent Manner ◽  
Mesenchymal Transition ◽  
Pc3 Cells ◽  
Gsk 3Β

Background: Wogonoside, an effective component of Scutellaria baicalensis extract, has recently become a hot topic for its newly discovered anticancer efficacy, but the underlying pharmacological mechanism is still unclear. In this study, we tested the inhibitory effects of wogonoside in human prostate cancer PC3 cells in vitro and vivo. Methods: The effects of wogonoside on cell viability, cycle progression, invasion, migration, and apoptosis were assessed in vitro. The levels of proteins in related signaling pathways were detected by western blotting assay. Finally, nude mouse tumorigenicity assay was conducted to detect the anticancer effect of wogonoside in vivo. Results: Wogonoside inhibited cell viability, invasive and migratory ability in a time- and dose-dependent manner. Flow cytometry indicated that wogonoside could induce cell apoptosis and S phase cell-cycle arrest. Mechanically, wogonoside suppressed the Wnt/β-catenin signaling pathway, and the level of p-glycogen synthase kinase-3β (GSK-3β; Ser9) was inhibited by wogonoside. The epithelial-mesenchymal transition (EMT) process was also reversed in PC3 cell line after wogonoside treatment. In vivo experiments showed that wogonoside inhibited tumor growth in xenograft mouse models. Conclusion: These findings revealed that wogonoside could suppress Wnt/β-catenin pathway and reversing the EMT process in PC3 cells. GSK-3β acts as a tumor suppressor in prostate cancer. Wogonoside may serve as an effective agent for treating prostate cancer.

scholarly journals Elevated Expression Levels of PC3-Secreted Microprotein (PSMP) in Prostate Cancer Associated With Increased Xenograft Growth and Modification of Immune-Related Microenvironment

2019 ◽  
Vol 9 ◽  
Author(s):  
Xiaolei Pei ◽  
Danfeng Zheng ◽  
Shaoping She ◽  
Zhiwei Fang ◽  
Shiying Zhang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Neutralizing Antibodies ◽  
Epithelial Mesenchymal Transition ◽  
Macrophage Polarization ◽  
Xenograft Model ◽  
Metastatic Progression ◽  
Male Mortality ◽  
Mesenchymal Transition ◽  
Monocyte Migration

Prostate cancer (PCa), especially metastatic PCa, is one of the main cancer types accounting for male mortality worldwide. Over decades, researchers have tried to search for effective curative methods for PCa, but many attempts have failed. The therapeutic failure of PCa is usually due to off-target or side effects; thus, finding a key molecule that could prevent PCa metastatic progression has become the most important goal for curing aggressive PCa. In this study, we collected hundreds of PCa tissues and serum and urine samples from patients to verify the upregulated expression of PC3-secreted microprotein (PSMP) in PCa tumor tissues with high Gleason scores. According to biopsy results, PSMP expression was found related to extraprostatic extension (EPE), contributing to PCa metastasis. Mechanistically, recombinant PSMP protein could promote the proliferation both in vitro and in vivo, and rhPSMP could promote epithelial–mesenchymal transition (EMT) of PC3 in vitro. Additionally, PSMP could also influence cytokine production in the xenograft model and monocyte migration and macrophage polarization in vitro. Our most important finding was that neutralizing antibodies against PSMP could suppress xenograft PC3 growth and promote the survival of PC3 metastatic mice model, providing an effective option to cure human PCa.

HEG1 indicates poor prognosis and promotes hepatocellular carcinoma invasion, metastasis, and EMT by activating Wnt/β-catenin signaling

2019 ◽  
Vol 133 (14) ◽  
pp. 1645-1662 ◽  
Author(s):  
Yan-rong Zhao ◽  
Ji-long Wang ◽  
Cong Xu ◽  
Yi-ming Li ◽  
Bo Sun ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Heart Development ◽  
Poor Prognosis ◽  
Nuclear Translocation ◽  
Epithelial Mesenchymal Transition ◽  
Disease Free Survival ◽  
Intrahepatic Metastasis ◽  
Mesenchymal Transition

Abstract Heart development protein with EGF-like domains 1 (HEG1) plays critical roles in embryo development and angiogenesis, which are closely related to tumor progression. However, the role of HEG1 in hepatocellular carcinoma (HCC) remains unknown. In the present study, we explored the clinical significance, biological function and regulatory mechanisms of HEG1 in HCC and found that HEG1 is significantly up-regulated in HCC cell lines and primary tumor samples. Additionally, high HEG1 expression is correlated with aggressive clinicopathological features. Patients with high HEG1 expression had shorter overall survival (OS) and disease-free survival (DFS) than those with low HEG1 expression, which indicated that HEG1 is an independent factor for poor prognosis. Lentivirus-mediated HEG1 overexpression significantly promotes HCC cell migration, invasion and epithelial–mesenchymal transition (EMT) in vitro and promotes intrahepatic metastasis, lung metastasis and EMT in vivo. Opposing results are observed when HEG1 is silenced. Mechanistically, HEG1 promotes β-catenin expression and maintains its stability, leading to intracellular β-catenin accumulation, β-catenin nuclear translocation and Wnt signaling activation. Loss- and gain-of-function assays further confirmed that β-catenin is essential for HEG1-mediated promotion of HCC invasion, metastasis and EMT. In conclusion, HEG1 indicates poor prognosis; plays important roles in HCC invasion, metastasis and EMT by activating Wnt/β-catenin signaling; and can serve as a potentially valuable prognostic biomarker and therapeutic target for HCC.

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 RNA N6-methyladenosine Reader IGF2BP2 Promotes Lymphatic Metastasis and Epithelial-mesenchymal Transition of Head and Neck Squamous Carcinoma Cells via Stabilizing Slug mRNA in an M6A-dependent Manner

2021 ◽  
Author(s):  
Dan Yu ◽  
Min Pan ◽  
Yanshi Li ◽  
Tao Lu ◽  
Zhihai Wang ◽  
...  
Keyword(s):  
Head And Neck ◽  
Mrna Stability ◽  
Lymphatic Metastasis ◽  
Poor Prognosis ◽  
Epithelial Mesenchymal Transition ◽  
Squamous Carcinoma ◽  
Mesenchymal Transition ◽  
Hnscc Cell

Abstract Background: Lymph node metastasis is the main cause of poor prognosis of head and neck squamous carcinoma (HNSCC) patients. N6-methyladenosine (m6A) RNA modification is an emerging epigenetic regulatory mechanism for gene expression, and as a novel m6A reader protein, IGF2BP2 has been implicated in tumor progression and metastasis. However, not much is currently known about the functional roles of IGF2BP2 in HNSCC, and whether IGF2BP2 regulates lymphatic metastasis through m6A modification in HNSCC remains to be determined. Methods: The expression and overall survival (OS) probability of m6A-related regulators in HNSCC were analyzed with The Cancer Genome Atlas (TCGA) dataset and GEPIA website tool, respectively. The expression levels of IGF2BP2 were measured in HNSCC tissues and normal adjacent tissues. To study the effects of IGF2BP2 on HNSCC cell metastasis in vitro and in vivo, gain- and loss- of function methods were employed. RIP, MeRIP, and luciferase reporter and mRNA stability assays were performed to explore the epigenetic mechanism of IGF2BP2 in HNSCC. Results: We investigated 20 m6A-related regulators in HNSCC and discovered that only the overexpression of IGF2BP2 was associated with a poor OS probability and an independent prognostic factor for HNSCC patients. Additionally, we demonstrated that IGF2BP2 was overexpressed in HNSCC tissues, and significantly correlated to lymphatic metastasis and poor prognosis. Functional studies have shown that IGF2BP2 promotes both HNSCC cell migration as well as invasion via the epithelial-mesenchymal transition (EMT) process in vitro, and IGF2BP2 knockdown significantly inhibited lymphatic metastasis and lymphangiogenesis in vivo. Mechanistic investigations revealed that Slug, a key EMT-related transcriptional factor, is the direct target of IGF2BP2, and essential for IGF2BP2-regulated EMT and metastasis in HNSCC. Furthermore, we demonstrated that IGF2BP2 recognizes and binds the m6A site in the coding sequence (CDS) region of Slug and promotes its mRNA stability. Conclusions: Collectively, our study uncovers the oncogenic role and potential mechanism of IGF2BP2, which serves as a m6A reader, in controlling lymphatic metastasis and EMT in HNSCC, suggesting that IGF2BP2 may act as a therapeutic target and prognostic biomarker for HNSCC patients with metastasis.

scholarly journals Upregulated Wnt-11 and miR-21 Expression Trigger Epithelial Mesenchymal Transition in Aggressive Prostate Cancer Cells

Biology ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 52 ◽  
Author(s):  
Elif Damla Arisan ◽  
Ozge Rencuzogullari ◽  
Ines Lua Freitas ◽  
Syanas Radzali ◽  
Buse Keskin ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Significant Inhibition ◽  
Developmentally Regulated ◽  
Tissue Samples ◽  
Mesenchymal Transition ◽  
Formalin Fixed Paraffin ◽  
Signaling Axis

Prostate cancer (PCa) is the second-leading cause of cancer-related death among men. microRNAs have been identified as having potential roles in tumorigenesis. An oncomir, miR-21, is commonly highly upregulated in many cancers, including PCa, and showed correlation with the Wnt-signaling axis to increase invasion. Wnt-11 is a developmentally regulated gene and has been found to be upregulated in PCa, but its mechanism is unknown. The present study aimed to investigate the roles of miR-21 and Wnt-11 in PCa in vivo and in vitro. First, different Gleason score PCa tissue samples were used; both miR-21 and Wnt-11 expressions correlate with high Gleason scores in PCa patient tissues. This data then was confirmed with formalin-fixed paraffin cell blocks using PCa cell lines LNCaP and PC3. Cell survival and colony formation studies proved that miR-21 involves in cells’ behaviors, as well as the epithelial-mesenchymal transition. Consistent with the previous data, silencing miR-21 led to significant inhibition of cellular invasiveness. Overall, these results suggest that miR-21 plays a significant role related to Wnt-11 in the pathophysiology of PCa.

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