An essential role for decorin in bladder cancer invasiveness

El-Behi, Mohamed; Krumeich, Sophie; Lodillinsky, Catalina; Kamoun, Aurélie; Tibaldi, Lorenzo; Sugano, Gaël; Reyniès, Aurélien de; Chapeaublanc, Élodie; Laplanche, Agnès; Lebrét, Thierry; Allory, Yves; Radvanyi, François; Lantz, Olivier; Eiján, Ana María; Bernard‐Pierrot, Isabelle; Théry, Clotilde

doi:10.1002/emmm.201302655

Cited by 45 publications

(33 citation statements)

References 59 publications

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“…Leygue et al 39 had shown in breast cancer and Suhovskih et al 40 in prostatic cancer that the mRNA expression of Decorin was significantly lower in tumour tissue compared with normal tissue. On the contrary to the report published by El Behi et al 41 that states overexpression of Decorin in muscle invasive bladder cancer, we observed a reduced protein expression of Decorin by IHC and western blotting in tumour tissue as compared with adjacent non-tumour tissue. Previously, Sainio et al 42 had shown a similar low stromal Decorin expression in areas rich in bladder cancer cells as compared with non-malignant bladder tissue, and Oda et al 43 had observed a reduced immunostaining in stroma of invasive cancer and in situ breast cancer as compared with normal breast tissue.…”

Section: Discussioncontrasting

confidence: 99%

Altered expression of small leucine-rich proteoglycans (Decorin, Biglycan and Lumican): Plausible diagnostic marker in urothelial carcinoma of bladder

et al. 2017

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Small leucine-rich proteoglycans are components of extracellular matrix that regulates neoplastic transformation. Among small leucine rich proteoglycans, Decorin, Biglycan and Lumican are most commonly implicated markers, and their expression is well studied in various malignancies. In this novel study, we have collectively evaluated expression of these three molecules in urothelial carcinoma of bladder. Thirty patients of confirmed untreated bladder cancer, 30 healthy controls for blood and 30 controls for adjacent non-tumour tissue were enrolled. Blood was collected from all subjects and tumour/adjacent normal tissue was obtained from the patients. Circulatory levels were estimated by enzyme-linked immunosorbent assay, relative messenger RNA expression by quantitative polymerase chain reaction and protein expression by immunohistochemistry and western-blotting. Circulatory levels of Biglycan (p = 0.0038) and Lumican (p < 0.0001) were significantly elevated, and that of Decorin (p < 0.0001) was significantly reduced in patients as compared with controls. Protein expression by immunohistochemistry and western-blotting showed elevated expression of Lumican and Biglycan and lower expression of Decorin in urothelial carcinoma of bladder. Quantitative polymerase chain reaction for messenger RNA expression from tissue specimens revealed significantly higher expression of Biglycan (p = 0.0008) and Lumican (p = 0.01) and lower expression of Decorin (p < 0.0001) in urothelial carcinoma of bladder. Out of all molecules receiver operating characteristic curve showed that the 0.207 ng/ml cut-off of serum Lumican provided optimum sensitivity (90.0%) and specificity (90.0%). Significant alteration of matrix small leucine-rich proteoglycans in urothelial carcinoma of bladder was observed. Higher expression of Lumican in Bladder cancer patients with the cut-off value of highest optimum sensitivity and specificity shows its importance as a potential non-invasive marker for early detection of UBC following further validation in large patient cohort.

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Section: Discussioncontrasting

confidence: 99%

Altered expression of small leucine-rich proteoglycans (Decorin, Biglycan and Lumican): Plausible diagnostic marker in urothelial carcinoma of bladder

et al. 2017

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“…Transcriptomic data obtained with Affymetrix U133plus2.0 DNA arrays for our CIT‐cohorts of bladder tumors, encompassing 82 NMIBCs and 85 MIBCs, were previously deposited on the publicly available ArrayExpress databases E‐MTAB‐1803 and E‐MTAB‐1940, respectively (El Behi et al , ; Biton et al , ; Rebouissou et al , ). RNA‐Seq data for an independent cohort of 416 tumors were available from ArrayExpress E‐MTAB‐4321 (Hedegaard et al , ).…”

Section: Methodsmentioning

confidence: 99%

An FGFR 3/ MYC positive feedback loop provides new opportunities for targeted therapies in bladder cancers

et al. 2018

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FGFR3 alterations (mutations or translocation) are among the most frequent genetic events in bladder carcinoma. They lead to an aberrant activation of FGFR3 signaling, conferring an oncogenic dependence, which we studied here. We discovered a positive feedback loop, in which the activation of p38 and AKT downstream from the altered FGFR3 upregulates MYC mRNA levels and stabilizes MYC protein, respectively, leading to the accumulation of MYC, which directly upregulates FGFR3 expression by binding to active enhancers upstream from FGFR3. Disruption of this FGFR3/MYC loop in bladder cancer cell lines by treatment with FGFR3, p38, AKT, or BET bromodomain inhibitors (JQ1) preventing MYC transcription decreased cell viability in vitro and tumor growth in vivo. A relevance of this loop to human bladder tumors was supported by the positive correlation between FGFR3 and MYC levels in tumors bearing FGFR3 mutations, and the decrease in FGFR3 and MYC levels following anti‐FGFR treatment in a PDX model bearing an FGFR3 mutation. These findings open up new possibilities for the treatment of bladder tumors displaying aberrant FGFR3 activation.

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“…Various mRNAs encoding collagen chain components were either up‐ ( COL8A1 , COL12A1 and COL28A1 ) or down‐regulated ( COL17A1 ). Of note, over‐expression of decorin , fibronectin 1 and collagen chains COL8A1 and COL12A1 has recently been shown to promote invasiveness of various cancer types. These results indicate that c‐Src(mt) significantly alters cell–matrix interactions, thereby decreasing cell adhesion and promoting cellular migration and invasiveness.…”

Section: Resultsmentioning

confidence: 99%

Transcriptional signature induced by a metastasis‐promoting c‐Src mutant in a human breast cell line

et al. 2016

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Deletions at the C-terminus of the proto-oncogene protein c-Src kinase are found in the viral oncogene protein v-Src as well as in some advanced human colon cancers. They are associated with increased kinase activity and cellular invasiveness. Here, we analyzed the mRNA expression signature of a constitutively active C-terminal mutant of c-Src, c-Src(mt), in comparison with its wild-type protein, c-Src(wt), in the human non-transformed breast epithelial cell line MCF-10A. We demonstrated previously that the mutant altered migratory and metastatic properties. Genome-wide transcriptome analysis revealed that c-Src(mt) de-regulated the expression levels of approximately 430 mRNAs whose gene products are mainly involved in the cellular processes of migration and adhesion, apoptosis and protein synthesis. 82.9% of these genes have previously been linked to cellular migration, while the others play roles in RNA transport and splicing processes, for instance. Consistent with the transcriptome data, cells expressing c-Src(mt), but not those expressing c-Src(wt), showed the capacity to metastasize into the lungs of mice in vivo. The mRNA expression profile of c-Src(mt)-expressing cells shows significant overlap with that of various primary human tumor samples, possibly reflecting elevated Src activity in some cancerous cells. Expression of c-Src(mt) led to elevated migratory potential. We used this model system to analyze the transcriptional changes associated with an invasive cellular phenotype. These genes and pathways de-regulated by c-Src(mt) may provide suitable biomarkers or targets of therapeutic approaches for metastatic cells. DATABASE: This project was submitted to the National Center for Biotechnology Information BioProject under ID PRJNA288540. The Illumina RNA-Seq reads are available in the National Center for Biotechnology Information Sequence Read Archive under study ID SRP060008 with accession numbers SRS977414 for MCF-10A cells, SRS977717 for mock cells, SRS978053 for c-Src(wt) cells and SRS978046 for c-Src(mt) cells

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An essential role for decorin in bladder cancer invasiveness

Cited by 45 publications

References 59 publications

Altered expression of small leucine-rich proteoglycans (Decorin, Biglycan and Lumican): Plausible diagnostic marker in urothelial carcinoma of bladder

Altered expression of small leucine-rich proteoglycans (Decorin, Biglycan and Lumican): Plausible diagnostic marker in urothelial carcinoma of bladder

An FGFR 3/ MYC positive feedback loop provides new opportunities for targeted therapies in bladder cancers

Transcriptional signature induced by a metastasis‐promoting c‐Src mutant in a human breast cell line

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