scholarly journals α-Actinin-4 Promotes the Progression of Prostate Cancer Through the Akt/GSK-3β/β-Catenin Signaling Pathway

2020 ◽  
Vol 8 ◽  
Author(s):  
Sungyeon Park ◽  
Minsoo Kang ◽  
Suhyun Kim ◽  
Hyoung-Tae An ◽  
Jan Gettemans ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Actin Binding ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Ablation Therapy ◽  
Androgen Ablation ◽  
Proliferation And Metastasis ◽  
Gsk 3Β ◽  
Androgen Ablation Therapy

The first-line treatment for prostate cancer (PCa) is androgen ablation therapy. However, prostate tumors generally recur and progress to androgen-independent PCa (AIPC) within 2–3 years. α-Actinin-4 (ACTN4) is an actin-binding protein that belongs to the spectrin gene superfamily and acts as an oncogene in various cancer types. Although ACTN4 is involved in tumorigenesis and the epithelial–mesenchymal transition of cervical cancer, the role of ACTN4 in PCa remains unknown. We found that the ACTN4 expression level increased during the transition from androgen-dependent PCa to AIPC. ACTN4 overexpression resulted in enhanced proliferation and motility of PCa cells. Increased β-catenin due to ACTN4 promoted the transcription of genes involved in proliferation and metastasis such as CCND1 and ZEB1. ACTN4-overexpressing androgen-sensitive PCa cells were able to grow in charcoal-stripped media. In contrast, ACTN4 knockdown using si-ACTN4 and ACTN4 nanobody suppressed the proliferation, migration, and invasion of AIPC cells. Results of the xenograft experiment revealed that the mice injected with LNCaPACTN4 cells exhibited an increase in tumor mass compared with those injected with LNCaPMock cells. These results indicate that ACTN4 is involved in AIPC transition and promotes the progression of PCa.

scholarly journals CHN1 promotes epithelial–mesenchymal transition via the Akt/GSK-3β/Snail pathway in cervical carcinoma

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Haoqi Zhao ◽  
Lan Wang ◽  
Shufang Wang ◽  
Xihua Chen ◽  
Min Liang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Lymph Node ◽  
Signaling Pathway ◽  
Cervical Carcinoma ◽  
Epithelial Mesenchymal Transition ◽  
Migration And Invasion ◽  
Xenograft Tumor ◽  
Mesenchymal Transition ◽  
Gsk 3Β ◽  
Related Proteins

Abstract Background Metastasis and invasion are crucial in determining the mortality of cervical carcinoma (CC) patients. The epithelial–mesenchymal transition (EMT) is now a universal explanation for the mechanisms of tumor metastasis. Α-chimeric protein (α-chimaerin, CHN1) plays an important role in the regulation of signal transduction and development. However, the molecular regulatory relationships between CHN1 and CC progression in relation to EMT have not yet been identified. Methods The expression of CHN1 in CC tissues, adjacent tissues, and lymph node metastases from CC patients was detected by immunohistochemistry. Upregulation and knockdown of CHN1 were achieved by transfection of CC cells. The effect of CHN1 on cell proliferation was determined by CCK-8 and plate clone formation assays. Changes in migration and invasion capabilities were evaluated using scratch migration and transwell invasion assays. The effect of CHN1 overexpression and interference on xenograft tumor growth was determined by tumor weight and pathological analyses. The expression of EMT-related mRNAs was measured by qRT-PCR in transfected CC cells. EMT-related proteins and Akt/GSK-3β/Snail signaling pathway-related proteins were also evaluated by western blotting. Results CHN1 was overexpressed in CC tissues and was associated with lymph node metastasis and low survival in CC patients. Overexpression of CHN1 promoted cell proliferation, migration, and invasion in CC cells. In contrast, silencing of CHN1 inhibited these phenomena. Overexpression of CHN1 promoted tumor formation in an in vivo xenograft tumor mouse model, with increased tumor volumes and weights. In addition, CHN1 induced the expression of EMT-related transcription factors, accompanied by the decreased expression of epithelial markers and increased expression of mesenchymal markers. The Akt/GSK-3β/Snail signaling pathway was activated by overexpression of CHN1 in vitro, and activation of this pathway was inhibited by the signaling pathway inhibitor LY294002. Conclusion These results suggest that CHN1 promotes the development and progression of cervical carcinoma via the Akt/GSK-3β/Snail pathway by inducing EMT.

scholarly journals Crosstalk Between Nuclear MET and SOX9/β-Catenin Correlates with Castration-Resistant Prostate Cancer

2014 ◽  
Vol 28 (10) ◽  
pp. 1629-1639 ◽  
Author(s):  
Yingqiu Xie ◽  
Wenfu Lu ◽  
Shenji Liu ◽  
Qing Yang ◽  
Brett S. Carver ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Combined Treatment ◽  
Castration Resistant Prostate Cancer ◽  
Ablation Therapy ◽  
Androgen Ablation ◽  
Castration Resistant ◽  
Activate Cell ◽  
Androgen Ablation Therapy

Castration-resistant prostate cancer (PCa) (CRPC) is relapse after various forms of androgen ablation therapy and causes a major mortality in PCa patients, yet the mechanism remains poorly understood. Here, we report the nuclear form of mesenchymal epithelial transition factor (nMET) is essential for CRPC. Specifically, nMET is remarkably increased in human CRPC samples compared with naïve samples. Androgen deprivation induces endogenous nMET and promotes cell proliferation and stem-like cell self-renewal in androgen-nonresponsive PCa cells. Mechanistically, nMET activates SRY (sex determining region Y)-box9, β-catenin, and Nanog homeobox and promotes sphere formation in the absence of androgen stimulus. Combined treatment of MET and β-catenin enhances the inhibition of PCa cell growth. Importantly, MET accumulation is detected in nucleus of recurrent prostate tumors of castrated Pten/Trp53 null mice, whereas MET elevation is predominantly found in membrane of naïve tumors. Our findings reveal for the first time an essential role of nMET association with SOX9/β-catenin in CRPC in vitro and in vivo, highlighting that nuclear RTK activate cell reprogramming to drive recurrence, and targeting nMET would be a new avenue to treat recurrent cancers.

scholarly journals β-Sitosterol and Gemcitabine Exhibit Synergistic Anti-pancreatic Cancer Activity by Modulating Apoptosis and Inhibiting Epithelial–Mesenchymal Transition by Deactivating Akt/GSK-3β Signaling

2019 ◽  
Vol 9 ◽  
Author(s):  
Zhang-qi Cao ◽  
Xue-xi Wang ◽  
Li Lu ◽  
Jing-wen Xu ◽  
Xiao-bin Li ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Human Cancer ◽  
Combined Treatment ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Gsk 3Β ◽  
Cancer Activity

β-sitosterol (BS), a major bioactive constituent present in plants, has shown potent anti-cancer activity against many human cancer cells, but its activity in pancreatic cancer (PC) cells has rarely been reported. Gemcitabine (GEM) is one of the first-line drugs for PC therapy, however, the treatment effect is not sustained due to prolonged drug resistance. In this study, we firstly studied the anti-PC activity and the mechanism of BS alone and in combination with GEM in vitro and in vivo. BS effectively inhibited the growth of PC cell lines by inhibiting proliferation, inducing G0/G1 phase arrest and apoptosis, suppressed the NF- kB activity, and increased expression of the protein Bax but decreased expression of the protein Bcl-2. Moreover, BS inhibited migration and invasion and downregulated epithelial–mesenchymal transition (EMT) markers and AKT/GSK-3β signaling pathways. Furthermore, the combination of BS and GEM exhibited a significant synergistic effect in MIAPaCa-2 and BXPC-3 cells. More importantly, the combined treatment with BS and GEM lead to significant growth inhibition of PC xenografts. Overall, our data revealed a promising treatment option for PC by the combination therapy of BS and GEM.

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 Claudin-7 Inhibits Proliferation and Metastasis in Salivary Adenoid Cystic Carcinoma Through Wnt/β-Catenin Signaling

2020 ◽  
Vol 29 ◽  
pp. 096368972094358
Author(s):  
Huan Ji ◽  
Xu Ding ◽  
Wei Zhang ◽  
Yang Zheng ◽  
Hongming Du ◽  
...  
Keyword(s):  
Adenoid Cystic Carcinoma ◽  
Epithelial Mesenchymal Transition ◽  
Tumor Formation ◽  
Biological Behavior ◽  
Migration And Invasion ◽  
Salivary Adenoid Cystic Carcinoma ◽  
Mesenchymal Transition ◽  
Adenoid Cystic ◽  
Proliferation And Metastasis ◽  
And Gender

The aim of this study was to investigate claudin-7 (CLDN7) expression in salivary adenoid cystic carcinoma (SACC) and its function in SACC cells. We determined CLDN7 expression in SACC tumors via immunohistochemistry and western blotting and evaluated the association between CLDN7 expression and clinicopathologic variables. Besides this, we constructed a stably transfected CLDN7 knockdown SACC-LM cell line via RNAi and assessed its biological behavior changes (cell viability, migration, and invasion). The correlation between CLDN7 and epithelial-mesenchymal transition (EMT) was analyzed. Additionally, a subcutaneous tumor formation model was used to assess SACC-LM cells tumorigenicity after the CLDN7 knockdown. In the present study, we found the CLDN7 expression of tumor group was lower than that in normal salivary glands and was significantly correlated with lymph node metastasis, recurrence, and gender. CLDN7 knockdown could add the proliferation and metastasis ability of SACC by regulating EMT through Wnt/β-catenin signaling pathway. In addition, CLDN7 knockdown in SACC promoted tumor growth in nude mice. CLDN7 inhibits cell proliferation and metastasis by inactivating the Wnt/β-catenin signaling in SACC. Thus, CLDN7 expression might be a useful marker to identify the potential for progression in SACC.

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