SPOCK1 promotes metastasis in pancreatic cancer via NF-κB-dependent epithelial-mesenchymal transition by interacting with IκB-α

2021 ◽  
Author(s):  
Xuelian Cui ◽  
Yixuan Wang ◽  
Weiqiang Lan ◽  
Shuhao Wang ◽  
Ying Cui ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Epithelial Mesenchymal Transition ◽  
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 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 Epithelial-mesenchymal transition as a therapeutic target for overcoming chemoresistance in pancreatic cancer

2017 ◽  
Vol 9 (1) ◽  
pp. 37 ◽  
Author(s):  
Omar Elaskalani ◽  
Norbaini Binti Abdol Razak ◽  
Marco Falasca ◽  
Pat Metharom
Keyword(s):  
Pancreatic Cancer ◽  
Therapeutic Target ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition

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.

scholarly journals Keratin 17 Suppresses Cell Proliferation and Epithelial-Mesenchymal Transition in Pancreatic Cancer

2020 ◽  
Vol 7 ◽  
Author(s):  
Yong Zeng ◽  
Min Zou ◽  
Yan Liu ◽  
Keting Que ◽  
Yunbing Wang ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cell Proliferation ◽  
Cancer Cell ◽  
Cell Cycle Progression ◽  
Pancreatic Cancer Cell ◽  
Epithelial Mesenchymal Transition ◽  
Migration And Invasion ◽  
Cancer Cell Proliferation ◽  
Cycle Progression ◽  
Mesenchymal Transition

Keratin 17 (K17), a member of type I acidic epithelial keratin family, has been reported to be upregulated in many malignant tumors and to be involved in promoting the development of tumors. However, the precise role of K17 in progression of pancreatic cancer is still unknown. In this study, we found that K17 expression was highly expressed in pancreatic cancer tissues and cell lines and that upregulated expression was associated with the pathological grade and poor prognosis. K17 expression served as an independent predictor of pancreatic cancer survival. Meanwhile, we showed that knocking down K17 induced pancreatic cancer cell proliferation, colony formation and tumor growth in xenografts in mice. However, K17 upregulation inhibited pancreatic cancer cell proliferation and colony formation. Further mechanistic study revealed that K17 knockdown promoted cell cycle progression by upregulating CyclinD1 expression and repressed cell apoptosis. However, K17 upregulation suppressed cell cycle progression by decreasing CyclinD1 expression, and induced apoptosis by increasing the levels of cleaved Caspase3. In addition, K17 knockdown promoted pancreatic cancer cell migration and invasion, but K17 upregulation suppressed cell migration and invasion. Moreover, knocking down K17 promoted epithelial-mesenchymal transition (EMT) in pancreatic cancer cell by inhibiting E-cadherin expression and inducing Vimentin expression, and the effects of K17 upregulation were opposite to that of K17downregulation. Taken together, our findings suggest that K17 functions as a potential tumor suppressor, even though it is upregulated in pancreatic cancer.

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