Loss of the Protein‐Tyrosine Phosphatase DEP‐1/PTPRJ Drives Meningioma Cell Motility

Petermann, Astrid; Haase, Daniela; Wetzel, Andrea; Balavenkatraman, Kamal K.; Tenev, Tencho; Gührs, Karl‐Heinz; Friedrich, Sabrina; Nakamura, Makoto; Mawrin, Christian; Böhmer, Frank‐D.

doi:10.1111/j.1750-3639.2010.00464.x

Cited by 44 publications

(37 citation statements)

References 53 publications

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“…Constructs for expression of GST-DEP-1 (wild type or C1239S cytoplasmic domain) fusion proteins in E. coli were described earlier (23). Expression in bacteria (strain Escherichia coli BL21) and purification of GST fusion proteins were performed by standard techniques.…”

Section: Methodsmentioning

confidence: 99%

Protein-tyrosine Phosphatase DEP-1 Controls Receptor Tyrosine Kinase FLT3 Signaling

Arora

Stopp

Böhmer

et al. 2011

Journal of Biological Chemistry

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Phosphorylation of wild type FLT3 and AML-associated mutant FLT3 was recently analyzed using site-specific phosphotyrosine antibodies (15). Interestingly, the phosphorylation pattern of the different FLT3 variants showed quantitative and also qualitative differences. Although FLT3-ITD or mutations in the kinase domain resulted in ligand-independent FLT3 autophosphorylation and signaling activity, the wild type receptor is only autophosphorylated in response to stimulation with its cytokine FL.Signaling of receptor tyrosine kinases is modulated by protein-tyrosine phosphatases (PTP) (16), and aberrations in PTP function play a role in carcinogenesis (17). Some PTP, notably SHP-2, have been found to positively influence growth-stimulatory signaling pathways, and mutations leading to gain-offunction of these PTP can potentially be oncogenic. It has been demonstrated that SHP-2 directly interacts with FLT3 in a phosphorylation-dependent manner via phosphotyrosine 599. Table S1. 1 To whom correspondence should be addressed. Tel.: 49-3641-9395634; Fax:49-3641-9395602; E-mail: joerg.mueller2@med.uni-jena.de.2 The abbreviations used are: AML, acute myeloid leukemia; PTP, proteintyrosine phosphatase; FL, FLT3 ligand; PLC␥, phospholipase C␥; ITD, internal tandem duplication; MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide.

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Section: Methodsmentioning

confidence: 99%

Protein-tyrosine Phosphatase DEP-1 Controls Receptor Tyrosine Kinase FLT3 Signaling

Arora

Stopp

Böhmer

et al. 2011

Journal of Biological Chemistry

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“…Three DNA markers, one within the NF2 gene and 2 flanking markers, were analyzed by PCR using 6-FAMlabeled fluorescent primers and 60 C anneal temperature (21). Primer sequences are listed in Supplementary Table S1.…”

Section: Analysis Of Loh In the Nf2 Genementioning

confidence: 99%

“…Therefore, we used an orthotopic model with IOMM-Lee cell implantation in the subarachnoid space of nude mice (21). MRI was suitable to monitor tumor growth (Fig.…”

Section: Meningioma Growth Inhibition By Temsirolimus In Vivomentioning

confidence: 99%

mTORC1 Inhibitors Suppress Meningioma Growth in Mouse Models

Pachow

Andrae

Kliese

et al. 2013

Clinical Cancer Research

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Purpose: To evaluate the mTORC1 (mammalian target of rapamycin complex 1) pathway in meningiomas and to explore mTORC1 as a therapeutic target in meningioma cell lines and mouse models.Experimental Design: Tissue microarrays (53 meningiomas of all WHO grades) were stained for phosphorylated polypeptides of mTOR, Akt, and the mTORC1 targets 4EBP1 and p70S6K, the latter being the consensus marker for mTORC1 activity. Expression of proteins and mRNAs was assessed by Western blotting and real-time PCR in 25 tumors. Cell lines Ben-Men-1 (benign), IOMM-Lee and KT21 (malignant), and pairs of merlin-positive or -negative meningioma cells were used to assess sensitivity toward mTORC1 inhibitors in methyl-tetrazolium and bromodeoxyuridine (BrdUrd) assays. The effect of temsirolimus (20 mg/kg daily) on tumor weight or MRI-estimated tumor volume was tested by treatment of eight nude mice (vs. 7 controls) carrying subcutaneous IOMM-Lee xenografts, or of eight (5) mice xenotransplanted intracranially with IOMM-Lee (KT21) cells in comparison to eight (5) untreated controls.Results: All components of the mTORC1 pathway were expressed and activated in meningiomas, independent of their WHO grade. A significant dosage-dependent growth inhibition by temsirolimus and everolimus was observed in all cell lines. It was slightly diminished by merlin loss. In the orthotopic and subcutaneous xenograft models, temsirolimus treatment resulted in about 70% growth reduction of tumors (P < 0.01), which was paralleled by reduction of Ki67 mitotic index (P < 0.05) and reduction of mTORC1 activity (p70S6K phosphorylation) within the tumors.Conclusion: mTORC1 inhibitors suppress meningioma growth in mouse models, although the present study did not measure survival.

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“…The siRNA against DEP-1 was described previously (Petermann et al 2011). The siRNA against claudin-4 was designed using siDirect (http://sidirect2.rnai.jp/, antisense: 5´-AAUACUUGGCGGAGU AAGGCU-3´; sense: 5´-CCUUACUCCGCCAAGUAUUCU-3´).…”

Section: Preparation Of Sirnamentioning

confidence: 99%

“…DEP-1 has diverse roles in signal transduction; it regulates migration, proliferation, and differentiation as well as cell adhesion (Balavenkatraman et al 2006;Petermann et al 2011). DEP-1 dephosphorylates tyrosine residues of ZO-1 and occludin in MCF10A human mammary epithelial cells, and its knockdown increases cell permeability at the TJs (Sallee and Burridge 2009).…”

Section: Introductionmentioning

confidence: 99%

The Mycotoxin Patulin Decreases Expression of Density-Enhanced Phosphatase-1 by Down-Regulating PPAR<i>γ</i> in Human Colon Cancer Cells

Katsuyama

Konno

Shimoyama

et al. 2014

Tohoku J. Exp. Med.

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Patulin is a mycotoxin that is found mainly in apple products and causes symptoms such as bleeding from the digestive tract and diarrhea. Efforts to elucidate the mechanism of its toxicity have focused on protein tyrosine phosphatases (PTPs), which regulate the function of tight junctions (TJs) in colon epithelial cells. Patulin reacts with the conserved cysteine residues in the catalytic domains of PTP isoforms. Treatment of Caco-2 human colon cancer cells, used as a colon epithelial model, with 50 µM patulin decreased the level of density-enhanced phosphatase-1 (DEP-1) protein to 30% of the control level after 6 h. The level of DEP-1 mRNA was also decreased during 24 h after treatment with patulin. Moreover, knockdown of DEP-1 increased the level of phosphorylated claudin-4. Destruction of TJs by patulin treatment was observed by immunostaining with an antibody against zonula occludens (ZO)-1. To better understand the mechanistic basis of the decrease in DEP-1 mRNA levels, we searched for a cis-element upstream of the DEP-1 gene and found an element responsive to the peroxisome proliferator-activated receptor gamma (PPARγ ) protein. Using a PPARγ-specific antibody, we showed a decrease in PPARγ abundance to 42% of the control level within 6 h after treatment with patulin. PPARγ has four cysteine residues that are involved in zinc finger formation. Our data suggest that DEP-1 affects TJ function and that PPARγ might control DEP-1 expression. Therefore, the toxicity of patulin to cellular functions might be attributable to its ability to down-regulate the expression of DEP-1 and PPARγ.

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Loss of the Protein‐Tyrosine Phosphatase DEP‐1/PTPRJ Drives Meningioma Cell Motility

Cited by 44 publications

References 53 publications

Protein-tyrosine Phosphatase DEP-1 Controls Receptor Tyrosine Kinase FLT3 Signaling

Protein-tyrosine Phosphatase DEP-1 Controls Receptor Tyrosine Kinase FLT3 Signaling

mTORC1 Inhibitors Suppress Meningioma Growth in Mouse Models

The Mycotoxin Patulin Decreases Expression of Density-Enhanced Phosphatase-1 by Down-Regulating PPAR<i>γ</i> in Human Colon Cancer Cells

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