scholarly journals The Role and Mechanism of Epithelial-to-Mesenchymal Transition in Prostate Cancer Progression

2017 ◽  
Vol 18 (10) ◽  
pp. 2079 ◽  
Author(s):  
U-Ging Lo ◽  
Cheng-Fan Lee ◽  
Ming-Shyue Lee ◽  
Jer-Tsong Hsieh
Keyword(s):  
Prostate Cancer ◽  
Cancer Progression ◽  
Epithelial To Mesenchymal Transition ◽  
Prostate Cancer Progression ◽  
Mesenchymal Transition

miRNA as regulators of prostate carcinogenesis and endocrine and chemoresistance

2021 ◽  
Vol 20 ◽  
Author(s):  
Zoran Culig
Keyword(s):  
Prostate Cancer ◽  
Cancer Progression ◽  
Epithelial To Mesenchymal Transition ◽  
Growth Factor Receptor ◽  
Mitogen Activated Protein Kinase ◽  
Therapeutic Effects ◽  
Androgen Independence ◽  
Mesenchymal Transition ◽  
Androgen Synthesis ◽  
Mitogen Activated Protein

: More therapy options are available for advanced prostate cancer, including novel inhibitors of androgen synthesis, anti-androgens, chemotherapeutics and targeted therapies. Although patients´ survival has been improved, management of castration therapy-resistant prostate cancer remains a challenge. Regulation of cellular events in cancer by small non-coding miRNAs is therefore an area of special interest. Overexpression of selected miRNA may lead to androgen independence and prostate cancer progression. miRNA may be considered also a biomarker in patients with prostate cancer. In contrast, diminished expression of tumor-suppressive miRNA in prostate cancer leads to enhanced proliferation, reduced apoptosis, increased migration, invasion and epithelial-to-mesenchymal transition. miRNA may be directly involved in regulation of chemosensitivity in prostate cancer. Experimental overexpression of selected miRNA in chemoresistant prostate cancer leads to inhibition of cellular stemness and epithelial-to-mesenchymal transition. Reduction of tumorsuppressive miRNA may also lead to hyperactivity of signaling pathways such as that of the epidermal growth factor receptor and mitogen-activated protein kinase. Although a considerable progress on miRNA research in prostate cancer has been achieved, therapeutic effects could be improved on the basis of development of novel delivery methods.

The relationship of HIF2 and the progression of PTEN-deficient mouse prostate tumors.

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 30-30
Author(s):  
W. Y. Kim ◽  
B. Zhou ◽  
G. Thomas
Keyword(s):  
Prostate Cancer ◽  
Cancer Cell ◽  
Cancer Progression ◽  
Prostate Cancer Cell ◽  
Deficient Mouse ◽  
Prostate Cancer Progression ◽  
Prostate Tumors ◽  
Mesenchymal Transition

30 Background: The hypoxia-inducible factor (HIF) transcription factor has already cemented its oncogenic role in the development of renal cell carcinoma (RCC). However, its role in the tumorigenesis of other solid tumors remains unspecificed. Our studies focus on a novel link between HIF and prostate carcinogenesis. Methods: Using both in vitro cell culture studies as well as in vivo studies (orthotopic xenograft and genetically engineered mouse models) we investigate the role of HIF in prostate cancer cell proliferation, invasion, and progression. Results: Both HIF1 and HIF2 appear to be necessary for the proliferation and invasion of prostate cancer cell lines in vitro. Preliminary analysis of a PTEN deficient mouse model of prostate cancer suggests that expression of a stabilized form of HIF2 promotes the development of a larger prostate tumor burden and a more aggressive histology (high grade prostate intraepithelial neoplasia [PIN] at earlier stages). Moreover, PTEN-deficient prostate tumors producing HIF2 are more proliferative and vascular and express increased levels of genes associated with epithelial to mesenchymal transition (EMT). Conclusions: There has been much interest in the role of angiogenesis and hypoxia in prostate cancer progression. Our preliminary data suggest that HIF2 is able to promote PTEN-deficient prostate cancer progression in mice by increasing proliferation, angiogenesis, and EMT. No significant financial relationships to disclose.

scholarly journals Skp2 and Slug Are Coexpressed in Aggressive Prostate Cancer and Inhibited by Neddylation Blockade

2021 ◽  
Vol 22 (6) ◽  
pp. 2844
Author(s):  
Alena Mickova ◽  
Gvantsa Kharaishvili ◽  
Daniela Kurfurstova ◽  
Mariam Gachechiladze ◽  
Milan Kral ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Progression ◽  
Epithelial To Mesenchymal Transition ◽  
Treatment Strategies ◽  
Therapy Resistance ◽  
Mesenchymal Transition ◽  
Slug Expression ◽  
Chemical Inhibition ◽  
Novel Treatment Strategies ◽  
E Cadherin

Prostate cancer (PCa) is the second leading cause of cancer-related deaths in men in Western countries, and there is still an urgent need for a better understanding of PCa progression to inspire new treatment strategies. Skp2 is a substrate-recruiting component of the E3 ubiquitin ligase complex, whose activity is regulated through neddylation. Slug is a transcriptional repressor involved in the epithelial-to-mesenchymal transition, which may contribute to therapy resistance. Although Skp2 has previously been associated with a mesenchymal phenotype and prostate cancer progression, the relationship with Slug deserves further elucidation. We have previously shown that a high Gleason score (≥8) is associated with higher Skp2 and lower E-cadherin expression. In this study, significantly increased expression of Skp2, AR, and Slug, along with E-cadherin downregulation, was observed in primary prostate cancer in patients who already had lymph node metastases. Skp2 was slightly correlated with Slug and AR in the whole cohort (Rs 0.32 and 0.37, respectively), which was enhanced for both proteins in patients with high Gleason scores (Rs 0.56 and 0.53, respectively) and, in the case of Slug, also in patients with metastasis to lymph nodes (Rs 0.56). Coexpression of Skp2 and Slug was confirmed in prostate cancer tissues by multiplex immunohistochemistry and confocal microscopy. The same relationship between these two proteins was observed in three sets of prostate epithelial cell lines (PC3, DU145, and E2) and their mesenchymal counterparts. Chemical inhibition of Skp2, but not RNA interference, modestly decreased Slug protein in PC3 and its docetaxel-resistant subline PC3 DR12. Importantly, chemical inhibition of Skp2 by MLN4924 upregulated p27 and decreased Slug expression in PC3, PC3 DR12, and LAPC4 cells. Novel treatment strategies targeting Skp2 and Slug by the neddylation blockade may be promising in advanced prostate cancer, as recently documented for other aggressive solid tumors.

scholarly journals CKB inhibits epithelial-mesenchymal transition and prostate cancer progression by sequestering and inhibiting AKT activation

Neoplasia ◽  
2021 ◽  
Vol 23 (11) ◽  
pp. 1147-1165
Author(s):  
Zheng Wang ◽  
Mohit Hulsurkar ◽  
Lijuan Zhuo ◽  
Jinbang Xu ◽  
Han Yang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Progression ◽  
Epithelial Mesenchymal Transition ◽  
Prostate Cancer Progression ◽  
Mesenchymal Transition ◽  
Akt Activation

scholarly journals Loss of SNAI2 in Prostate Cancer Correlates With Clinical Response to Androgen Deprivation Therapy

2021 ◽  
pp. 1048-1059
Author(s):  
Marek Cmero ◽  
Natalie J. Kurganovs ◽  
Ryan Stuchbery ◽  
Patrick McCoy ◽  
Corrina Grima ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Response ◽  
Cancer Progression ◽  
Epithelial To Mesenchymal Transition ◽  
Treatment Resistance ◽  
Response To Therapy ◽  
Secondary Outcome ◽  
Short Term ◽  
Short Term Treatment ◽  
Mesenchymal Transition

PURPOSE Androgen receptor (AR) signaling is important in prostate cancer progression, and therapies that target this pathway have been the mainstay of treatment for advanced disease for over 70 years. Tumors eventually progress despite castration through a number of well-characterized mechanisms; however, little is known about what determines the magnitude of response to short-term pathway inhibition. METHODS We evaluated a novel combination of AR-targeting therapies (degarelix, abiraterone, and bicalutamide) and noted that the objective patient response to therapy was highly variable. To investigate what was driving treatment resistance in poorly responding patients, as a secondary outcome we comprehensively characterized pre- and post-treatment samples using both whole-genome and RNA sequencing. RESULTS We find that resistance following short-term treatment differs molecularly from typical progressive castration-resistant disease, associated with transcriptional reprogramming, to a transitional epithelial-to-mesenchymal transition (EMT) phenotype rather than an upregulation of AR signaling. Unexpectedly, tolerance to therapy appears to be the default state, with treatment response correlating with the prevalence of tumor cells deficient for SNAI2, a key regulator of EMT reprogramming. CONCLUSION We show that EMT characterizes acutely resistant prostate tumors and that deletion of SNAI2, a key transcriptional regulator of EMT, correlates with clinical response.

scholarly journals Functional Linkage of RKIP to the Epithelial to Mesenchymal Transition and Autophagy during the Development of Prostate Cancer

Cancers ◽  
2018 ◽  
Vol 10 (8) ◽  
pp. 273 ◽  
Author(s):  
Mahmoud Ahmed ◽  
Trang Lai ◽  
Sahib Zada ◽  
Jin Hwang ◽  
Trang Pham ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Progression ◽  
Cancer Metastasis ◽  
Epithelial To Mesenchymal Transition ◽  
Metastatic Cancer ◽  
Critical Role ◽  
Gene Products ◽  
Prostate Hyperplasia ◽  
Mesenchymal Transition ◽  
Novel Interactions

Raf kinase inhibitor protein (RKIP) plays a critical role in many signaling pathways as a multi-functional adapter protein. In particular, the loss of RKIP’s function in certain types of cancer cells results in epithelial to mesenchymal transition (EMT) and the promotion of cancer metastasis. In addition, RKIP inhibits autophagy by modulating LC3-lipidation and mTORC1. How the RKIP-dependent inhibition of autophagy is linked to EMT and cancer progression is still under investigation. In this study, we investigated the ways by which RKIP interacts with key gene products in EMT and autophagy during the progression of prostate cancer. We first identified the gene products of interest using the corresponding gene ontology terms. The weighted-gene co-expression network analysis (WGCNA) was applied on a gene expression dataset from three groups of prostate tissues; benign prostate hyperplasia, primary and metastatic cancer. We found two modules of highly co-expressed genes, which were preserved in other independent datasets of prostate cancer tissues. RKIP showed potentially novel interactions with one EMT and seven autophagy gene products (TGFBR1; PIK3C3, PIK3CB, TBC1D25, TBC1D5, TOLLIP, WDR45 and WIPI1). In addition, we identified several upstream transcription modulators that could regulate the expression of these gene products. Finally, we verified some RKIP novel interactions by co-localization using the confocal microscopy analysis in a prostate cancer cell line. To summarize, RKIP interacts with EMT and autophagy as part of the same functional unit in developing prostate cancer.

Sign in / Sign up

Export Citation Format

Share Document