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

Lo, U‐Ging; Lee, Cheng‐Fan; Lee, Ming-Shyue; Hsieh, Jer‐Tsong

doi:10.3390/ijms18102079

Cited by 100 publications

(78 citation statements)

References 148 publications

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“…Snail, Slug, Twist1, ZEB1, and ZEB2 are transcriptional regulators of EMT which regulates the expression of E‐Cadherin, Vimentin, and N‐cadherin. Snail and Slug are zinc finger transcription factors that belong to SNAI family which are dominant regulators of EMT in many cancers including PCa (Ganesan, Mallets, & Gomez‐Cambronero, ; Lo, Lee, Lee, & Hsieh, ). Results from this study revealed that overexpression of the VCP is associated with upregulation of Snail and Slug transcription factors and elevated Vimentin and decreased E‐cadherin expression correlating to EMT of cancer cells.…”

Section: Discussionmentioning

confidence: 99%

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Interleukin‐6 induced overexpression of valosin‐containing protein (VCP)/p97 is associated with androgen‐independent prostate cancer (AIPC) progression

Duscharla

Reddy

Dasari

et al. 2018

Journal Cellular Physiology

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Though Androgen deprivation therapy (ADT) is effective initially, numerous patients become resistant to it and develop castration resistant PCa (CRPC). Cytokines promotes ligand independent activation of AR. Interleukin-6 (IL-6) levels are elevated in CRPC patients and regulate AR activity. However, progression to CRPC is not fully understood. In this study, we analyzed differential protein expression in LNCaP cells treated with IL-6 using proteomics. Results revealed altered expression of 27 proteins and Valosin-containing protein (VCP)/p97 plays a predominant role in co-regulation of altered proteins. Interestingly, IL-6 induced VCP expression through Pim-1 via STAT3 is AR independent there by suggesting a role for VCP in CRPC. Transfection of LNCaP cells for VCP overexpression showed an increased cell proliferation, migration, and invasion where as its inhibition by NMS-873 showed the reverse effect causing cell death. Mechanistic studies demonstrate that cell death occurs due to apoptosis by endoplasmic reticulum (ER) stress, elevated cell cycle inhibitors p21, p27kip1, and active PARP and reduced Bcl-2. VCP promotes cell invasion and migration by altering E-cadherin and Vimentin levels inversely triggering EMT of PCa cells. VCP immunostaining revealed no staining in BPH but strong staining in PCa. This study determines VCP may play an important role in progression to CRPC and it can be a favorable target with to develop new therapies to treat ADT resistant prostate cancer.

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Section: Discussionmentioning

confidence: 99%

“…Cadherin, Vimentin, and N-cadherin. Snail and Slug are zinc finger transcription factors that belong to SNAI family which are dominant regulators of EMT in many cancers including PCa(Ganesan, Mallets, & Gomez-Cambronero, 2016;Lo, Lee, Lee, & Hsieh, 2017).…”

mentioning

confidence: 99%

Interleukin‐6 induced overexpression of valosin‐containing protein (VCP)/p97 is associated with androgen‐independent prostate cancer (AIPC) progression

Duscharla

Reddy

Dasari

et al. 2018

Journal Cellular Physiology

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“…Increasing evidences suggest that EMT plays a role in the regulation of PCSCs, metastatic ability and therapy resistance of PCa cells, reviewed in [101]. A number of different factors might contribute to EMT in PCa including autocrine and paracrine signaling molecules released by tumor cells and stroma, for example, transforming growth factor beta 1 (TGF-β1), fibroblast growth factor (FGF), interleukin 6 (IL-6), hypoxia-inducible factor (HIF), and Wnt ligands as reviewed previously [102]. EMT can also be triggered by anticancer therapy including ADT, chemotherapy, and radiotherapy.…”

Section: Epithelial-mesenchymal Transition and Pcscsmentioning

confidence: 99%

Concise Review: Prostate Cancer Stem Cells: Current Understanding

et al. 2018

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Prostate cancer (PCa) is heterogeneous, harboring phenotypically diverse cancer cell types. PCa cell heterogeneity is caused by genomic instability that leads to the clonal competition and evolution of the cancer genome and by epigenetic mechanisms that result in subclonal cellular differentiation. The process of tumor cell differentiation is initiated from a population of prostate cancer stem cells (PCSCs) that possess many phenotypic and functional properties of normal stem cells. Since the initial reports on PCSCs in 2005, there has been much effort to elucidate their biological properties, including unique metabolic characteristics. In this Review, we discuss the current methods for PCSC enrichment and analysis, the hallmarks of PCSC metabolism, and the role of PCSCs in tumor progression. Stem Cells 2018;36:1457-1474.

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“…It is a complex mechanism which involves modification of various signaling pathways. These pathways are regulated by several transcriptional factors, notably SNAIL, Zinc finger protein SNAI2(SLUG), TWIST 1/2 , ZEB 1/2 [118]. In PCa, miRNAs have been shown to induce EMT by regulating these transcription factors directly [119,120].…”

Section: Mirna During the Epithelial-mesenchymal Transition (Emt)mentioning

confidence: 99%

microRNAs identified in prostate cancer: Correlative studies on response to ionizing radiation

et al. 2020

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As the most frequently diagnosed non-skin cancer in men and a leading cause of cancer-related death, understanding the molecular mechanisms that drive treatment resistance in prostate cancer poses a significant clinical need. Radiotherapy is one of the most widely used treatments for prostate cancer, along with surgery, hormone therapy, and chemotherapy. However, inherent radioresistance of tumor cells can reduce local control and ultimately lead to poor patient outcomes, such as recurrence, metastasis and death. The underlying mechanisms of radioresistance have not been fully elucidated, but it has been suggested that miRNAs play a critical role. miRNAs are small non-coding RNAs that regulate gene expression in every signaling pathway of the cell, with one miRNA often having multiple targets. By fine-tuning gene expression, miRNAs are important players in modulating DNA damage response, cell death, tumor aggression and the tumor microenvironment, and can ultimately affect a tumor's response to radiotherapy. Furthermore, much interest has focused on miRNAs found in biofluids and their potential utility in various clinical applications. In this review, we summarize the current knowledge on miRNA deregulation after irradiation and the associated functional outcomes, with a focus on prostate cancer. In addition, we discuss the utility of circulating miRNAs as non-invasive biomarkers to diagnose, predict response to treatment, and prognosticate patient outcomes.

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

Cited by 100 publications

References 148 publications

Interleukin‐6 induced overexpression of valosin‐containing protein (VCP)/p97 is associated with androgen‐independent prostate cancer (AIPC) progression

Interleukin‐6 induced overexpression of valosin‐containing protein (VCP)/p97 is associated with androgen‐independent prostate cancer (AIPC) progression

Concise Review: Prostate Cancer Stem Cells: Current Understanding

microRNAs identified in prostate cancer: Correlative studies on response to ionizing radiation

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