Cadherin-11 Is a Cell Surface Marker Up-Regulated in Activated Pancreatic Stellate Cells and Is Involved in Pancreatic Cancer Cell Migration

Birtolo, Chiara; Pham, Hung; Morvaridi, Susan; Chheda, Chintan; Go, Vay Liang W.; Ptasznik, Andrzej; Edderkaoui, Mouad; Weisman, Michael H.; Noss, Erika H.; Brenner, Michael B.; Larson, Brent K.; Guindi, Maha; Wang, Qiang; Pandol, Stephen J.

doi:10.1016/j.ajpath.2016.09.012

Cited by 39 publications

(24 citation statements)

References 61 publications

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“…Furthermore, expression of the β‐catenin target genes Axin2 , LEF1 , NKD1 , and NKD2 was completely abolished in the MTPa‐Tspan8 cells, indicating modulation of β‐catenin signalling upon Tspan8 overexpression (Figure A). On the protein levels, E‐cadherin and Tspan8 were significantly increased, while p120‐catenin and cadherin‐11, the regulators of mesenchymal cell properties , were significantly decreased in the MTPa‐Tspan8 cells, supporting the notion that Tspan8 mediated MET (Figure B). Using immunofluorescence, we observed membrane localisation of Tspan8 and E‐cadherin in the MTPa‐Tspan8 cells (Figure C).…”

Section: Resultssupporting

confidence: 61%

Tspan8 is expressed in breast cancer and regulates E‐cadherin/catenin signalling and metastasis accompanied by increased circulating extracellular vesicles

Voglstaetter

Thomsen

Nouvel

et al. 2019

The Journal of Pathology

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Tspan8 exhibits a functional role in many cancer types including pancreatic, colorectal, oesophagus carcinoma, and melanoma. We present a first study on the expression and function of Tspan8 in breast cancer. Tspan8 protein was present in the majority of human primary breast cancer lesions and metastases in the brain, bone, lung, and liver. In a syngeneic rat breast cancer model, Tspan8+ tumours formed multiple liver and spleen metastases, while Tspan8− tumours exhibited a significantly diminished ability to metastasise, indicating a role of Tspan8 in metastases. Addressing the underlying molecular mechanisms, we discovered that Tspan8 can mediate up‐regulation of E‐cadherin and down‐regulation of Twist, p120‐catenin, and β‐catenin target genes accompanied by the change of cell phenotype, resembling the mesenchymal–epithelial transition. Furthermore, Tspan8+ cells exhibited enhanced cell–cell adhesion, diminished motility, and decreased sensitivity to irradiation. As a regulator of the content and function of extracellular vesicles (EVs), Tspan8 mediated a several‐fold increase in EV number in cell culture and the circulation of tumour‐bearing animals. We observed increased protein levels of E‐cadherin and p120‐catenin in these EVs; furthermore, Tspan8 and p120‐catenin were co‐immunoprecipitated, indicating that they may interact with each other. Altogether, our findings show the presence of Tspan8 in breast cancer primary lesion and metastases and indicate its role as a regulator of cell behaviour and EV release in breast cancer. © 2019 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

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Section: Resultssupporting

confidence: 61%

Tspan8 is expressed in breast cancer and regulates E‐cadherin/catenin signalling and metastasis accompanied by increased circulating extracellular vesicles

Voglstaetter

Thomsen

Nouvel

et al. 2019

The Journal of Pathology

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“…Furthermore, CDH11 expression was linked with many pathologic processes, such as inflammation and fibrosis, which played an important role in the progression from chronic inflammation to cancer. 23 , 29 In addition, CDH11 has been implicated in prostate, breast and colorectal cancer metastases. 30 – 32 …”

Section: Discussionmentioning

confidence: 99%

Co-expression network analysis identified CDH11 in association with progression and prognosis in gastric cancer

Chen¹,

Wang²,

Nie³

et al. 2018

OTT

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Background and aimsGastric cancer (GC) is one of the most common cancers worldwide, and its pathogenesis is related to a complex network of gene interactions. The aims of our study were to find hub genes associated with the progression and prognosis of GC and illustrate the underlying mechanisms.MethodsWeighted gene co-expression network analysis (WGCNA) was conducted using the microarray dataset and clinical data of GC patients from Gene Expression Omnibus (GEO) database to identify significant gene modules and hub genes associated with TNM stage in GC. Functional enrichment analysis and protein–protein interaction network analysis were performed using the significant module genes. We regarded the common hub genes in the co-expression network and protein–protein interaction (PPI) network as “real” hub genes for further analysis. Hub gene was validated in another independent dataset and The Cancer Genome Atlas (TCGA) dataset.ResultsIn the significant purple module (R2=0.35), a total of 12 network hub genes were identified, among which six were also hub nodes in the PPI network of the module genes. Functional annotation revealed that the genes in the purple module focused on the biological processes of system development, biological adhesion, extracellular structure organization and metabolic process. In terms of validation, CDH11 had a higher correlation with the TNM stage than other hub genes and was strongly correlated with biological adhesion based on GO functional enrichment analysis. Data obtained from the Gene Expression Profiling Interactive Analysis (GEPIA) showed that CDH11 expression had a strong positive correlation with GC stages (P<0.0001). In the testing set and Oncomine dataset, CDH11 was highly expressed in GC tissues (P<0.0001). Survival analysis indicated that samples with a high CDH11 expression showed a poor prognosis. Cox regression analysis demonstrated an independent predictor of CDH11 expression in GC prognosis (HR=1.482, 95% CI: 1.015–2.164). Furthermore, gene set enrichment analysis (GSEA) demonstrated that multiple tumor-related pathways, especially focal adhesion, were enriched in CDH11 highly expressed samples.ConclusionCDH11 was identified and validated in association with progression and prognosis in GC, probably by regulating biological adhesion and focal adhesion-related pathways.

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“…S100A4, another new bio-marker for activated PSCs, has been reported in murine pancreatic cancer-related fibroblasts ( Farrow et al, 2009 ; Zechner et al, 2014 ). Birtolo et al (2017) discovered that cadherin-11 was also up-regulated in activated PSCs. And its mediated cell adhesion and TGF-β signaling participated in cancer cell migration involved in the spread and metastasis of pancreatic cancer.…”

Section: The Functional Heterogeneity Of Pscsmentioning

confidence: 99%

A Rising Star in Pancreatic Diseases: Pancreatic Stellate Cells

et al. 2018

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Pancreatic stellate cell (PSC) is a type of pluripotent cell located between pancreatic lobules and the surrounding area of acinars. When activated, PSC can be transformed into myofibroblast-like cell. A number of evidences suggest that activated PSC is the main source of the accumulation of extracellular matrix (ECM) protein under the pathological conditions, which lead to pancreatic fibrosis in chronic pancreatitis and pancreatic cancer. Recent studies have found that PSC also plays an important role in the endocrine cell function, islet fibrosis and diabetes. In order to provide new strategies for the treatment of pancreatic diseases, this paper systematically summarizes the recent researches about the biological behaviors of PSC, including its stem/progenitor cell characteristics, secreted exosomes, cellular senescence, epithelial mesenchymal transformation (EMT), energy metabolism and direct mechanical reprogramming.

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Cadherin-11 Is a Cell Surface Marker Up-Regulated in Activated Pancreatic Stellate Cells and Is Involved in Pancreatic Cancer Cell Migration

Cited by 39 publications

References 61 publications

Tspan8 is expressed in breast cancer and regulates E‐cadherin/catenin signalling and metastasis accompanied by increased circulating extracellular vesicles

Tspan8 is expressed in breast cancer and regulates E‐cadherin/catenin signalling and metastasis accompanied by increased circulating extracellular vesicles

Co-expression network analysis identified CDH11 in association with progression and prognosis in gastric cancer

A Rising Star in Pancreatic Diseases: Pancreatic Stellate Cells

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