Iron Chelation: Inhibition of Key Signaling Pathways in the Induction of the Epithelial Mesenchymal Transition in Pancreatic Cancer and Other Tumors

2013 ◽  
Vol 18 (5) ◽  
pp. 409-434 ◽  
Author(s):  
Alexander Richardson ◽  
Zaklina Kovacevic ◽  
Des R. Richardson
Keyword(s):  
Pancreatic Cancer ◽  
Signaling Pathways ◽  
Epithelial Mesenchymal Transition ◽  
Iron Chelation ◽  
Mesenchymal Transition

scholarly journals Long noncoding RNA LINC00941 promotes pancreatic cancer progression by competitively binding miR-335-5p to regulate ROCK1-mediated LIMK1/Cofilin-1 signaling

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jie Wang ◽  
Zhiwei He ◽  
Jian Xu ◽  
Peng Chen ◽  
Jianxin Jiang
Keyword(s):  
Pancreatic Cancer ◽  
Cell Growth ◽  
Cell Lines ◽  
Cancer Progression ◽  
Noncoding Rna ◽  
Epithelial Mesenchymal Transition ◽  
Loss Of Function ◽  
Mesenchymal Transition

AbstractAn accumulation of evidence indicates that long noncoding RNAs are involved in the tumorigenesis and progression of pancreatic cancer (PC). In this study, we investigated the functions and molecular mechanism of action of LINC00941 in PC. Quantitative PCR was used to examine the expression of LINC00941 and miR-335-5p in PC tissues and cell lines, and to investigate the correlation between LINC00941 expression and clinicopathological features. Plasmid vectors or lentiviruses were used to manipulate the expression of LINC00941, miR-335-5p, and ROCK1 in PC cell lines. Gain or loss-of-function assays and mechanistic assays were employed to verify the roles of LINC00941, miR-335-5p, and ROCK1 in PC cell growth and metastasis, both in vivo and in vitro. LINC00941 and ROCK1 were found to be highly expressed in PC, while miR-335-5p exhibited low expression. High LINC00941 expression was strongly associated with larger tumor size, lymph node metastasis, and poor prognosis. Functional experiments revealed that LINC00941 silencing significantly suppressed PC cell growth, metastasis and epithelial–mesenchymal transition. LINC00941 functioned as a molecular sponge for miR-335-5p, and a competitive endogenous RNA (ceRNA) for ROCK1, promoting ROCK1 upregulation, and LIMK1/Cofilin-1 pathway activation. Our observations lead us to conclude that LINC00941 functions as an oncogene in PC progression, behaving as a ceRNA for miR-335-5p binding. LINC00941 may therefore have potential utility as a diagnostic and treatment target in this disease.

scholarly journals Pancreatic Cancers with High Grade Tumor Budding Exhibit Hallmarks of Diminished Anti-Tumor Immunity

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1090
Author(s):  
Hassan Sadozai ◽  
Animesh Acharjee ◽  
Thomas Gruber ◽  
Beat Gloor ◽  
Eva Karamitopoulou
Keyword(s):  
Gene Expression ◽  
Pancreatic Cancer ◽  
Disease Progression ◽  
Immune Escape ◽  
Epithelial Mesenchymal Transition ◽  
Tumor Budding ◽  
Ductal Adenocarcinoma ◽  
Low Grade ◽  
High Grade ◽  
Mesenchymal Transition

Tumor budding is associated with epithelial-mesenchymal transition and diminished survival in a number of cancer types including pancreatic ductal adenocarcinoma (PDAC). In this study, we dissect the immune landscapes of patients with high grade versus low grade tumor budding to determine the features associated with immune escape and disease progression in pancreatic cancer. We performed immunohistochemistry-based quantification of tumor-infiltrating leukocytes and tumor bud assessment in a cohort of n = 111 PDAC patients in a tissue microarray (TMA) format. Patients were divided based on the ITBCC categories of tumor budding as Low Grade (LG: categories 1 and 2) and High Grade (HG: category 3). Tumor budding numbers and tumor budding grade demonstrated a significant association with diminished overall survival (OS). HG cases exhibit notably reduced densities of stromal (S) and intratumoral (IT) T cells. HG cases also display lower M1 macrophages (S) and increased M2 macrophages (IT). These findings were validated using gene expression data from TCGA. A published tumor budding gene signature demonstrated a significant association with diminished survival in PDAC patients in TCGA. Immune-related gene expression revealed an immunosuppressive TME in PDAC cases with high expression of the budding signature. Our findings highlight a number of immune features that permit an improved understanding of disease progression and EMT in pancreatic cancer.

scholarly journals The Molecular Mechanism of Epithelial–Mesenchymal Transition for Breast Carcinogenesis

Biomolecules ◽  
2019 ◽  
Vol 9 (9) ◽  
pp. 476 ◽  
Author(s):  
Chia-Jung Li ◽  
Pei-Yi Chu ◽  
Giou-Teng Yiang ◽  
Meng-Yu Wu
Keyword(s):  
Epithelial Cells ◽  
Tumor Progression ◽  
Signaling Pathways ◽  
Intracellular Signaling ◽  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Epithelial Mesenchymal Transition ◽  
Transforming Growth Factor Β ◽  
Inhibition Of Proliferation ◽  
Mesenchymal Transition

The transforming growth factor-β (TGF-β) signaling pathway plays multiple regulatory roles in the tumorigenesis and development of cancer. TGF-β can inhibit the growth and proliferation of epithelial cells and induce apoptosis, thereby playing a role in inhibiting breast cancer. Therefore, the loss of response in epithelial cells that leads to the inhibition of cell proliferation due to TGF-β is a landmark event in tumorigenesis. As tumors progress, TGF-β can promote tumor cell invasion, metastasis, and drug resistance. At present, the above-mentioned role of TGF-β is related to the interaction of multiple signaling pathways in the cell, which can attenuate or abolish the inhibition of proliferation and apoptosis-promoting effects of TGF-β and enhance its promotion of tumor progression. This article focuses on the molecular mechanisms through which TGF-β interacts with multiple intracellular signaling pathways in tumor progression and the effects of these interactions on tumorigenesis.

scholarly journals Caveolin-1 promotes pancreatic cancer cell differentiation and restores membranous E-cadherin via suppression of the epithelial-mesenchymal transition

Cell Cycle ◽  
2011 ◽  
Vol 10 (21) ◽  
pp. 3692-3700 ◽  
Author(s):  
Ahmed F. Salem ◽  
Gloria Bonuccelli ◽  
Generoso Bevilacqua ◽  
Hwyda Arafat ◽  
Richard G. Pestell ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cell Differentiation ◽  
Cancer Cell ◽  
Pancreatic Cancer Cell ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Caveolin 1 ◽  
E Cadherin

scholarly journals LncRNA-ZFAS1 Induces Epithelial-Mesenchymal Transition of Pancreatic Cancer Cells During Nutrient Deprivation by Promoting AMPK-Mediated Phosphorylation and Stabilization Of ZEB1 Protein

2021 ◽  
Author(s):  
ZHU ZENG ◽  
Shengbo Han ◽  
Yang Wang ◽  
Yan Huang ◽  
Yuhang Hu ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Nutrient Deprivation ◽  
Loss Of Function ◽  
Western Blot Assay ◽  
Normal Medium ◽  
Mesenchymal Transition ◽  
Glucose Depletion ◽  
Pancreatic Cancer Cells ◽  
Glutamine Deprivation

Abstract Background: Nutrient deprivation is a distinct feature of the tumor microenvironment that plays a crucial role in various cancers. However, the contribution and regulatory mechanism of nutrient deprivation on metastasis of pancreatic cancer (PC) have not been identified. Methods: PC cells were treated with normal medium, glucose-depletion or glutamine-depletion medium to observe the epithelial-mesenchymal transition (EMT). RT-qPCR and western blot assay were applied to evaluate the alteration of mRNA and protein of zinc finger E-box binding homeobox 1 (ZEB1), a crucial EMT regulator factor. Co-IP assay was utilized for evaluating the interaction between AMP-activated protein kinase (AMPK) and ZEB1. LncRNA microarray was adopted to detect the potential lncRNA, which facilitates the association between AMPK and ZEB1. Gain- and loss-of-function experiments were performed to evaluate the roles of ZNFX1 antisense RNA 1 (ZFAS1) in EMT and metastasis of PC. Results: The present study reveals that nutrient deprivation including glucose and glutamine deprivation significantly induces EMT of PC cells, which is dependent on stabilization of ZEB1. We further discover that nutrient deprivation induces upregulation of lncRNA ZFAS1, which promotes the association between AMPK and ZEB1 to phosphorylate and stabilize ZEB1 protein. Notably, ZEB1 reciprocally promotes the transcription of ZFAS1 by binding to the promoter of ZFAS1, forming feedback with ZFAS1. Consistently, depletion of ZFAS1 obviously inhibits nutrient deprivation-induced EMT of PC cells and lung metastasis of PC in nude mice. Meanwhile, clinical data displays that ZFAS1 is overexpressed in PC tissues and correlated with high expression of ZEB1 and Vimentin (VIM), low expression of E-cadherin (E-cad), as well as poor prognosis in PC patients. Conclusions: Our study implicates that glucose and glutamine deprivation promotes EMT and metastasis of PC through lncRNA-mediated stabilization of ZEB1.

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