PTPD1 Supports Receptor Stability and Mitogenic Signaling in Bladder Cancer Cells

Carlucci, Annalisa; Porpora, Monia; Garbi, Corrado; Galgani, Mario; Santoriello, Margherita; Mascolo, Massimo; Lorenzo, Domenico di; Altieri, Vincenzo; Quarto, Maria; Terracciano, Luigi; Gottesman, Max E.; Insabato, Luigi; Feliciello, Antonio

doi:10.1074/jbc.m110.174706

Cited by 49 publications

(46 citation statements)

References 37 publications

(46 reference statements)

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“…Cardone et al reported that PTPN21 is recruited to mitochondria by binding the scaffold protein AKAP121 and that this interaction is essential for the phosphatase dependent dephosphorylation of the inhibitory tyrosine 527 of the SRC kinase (Cardone et al, 2004; Carlucci et al, 2010). …”

Section: Resultsmentioning

confidence: 99%

Combining affinity proteomics and network context to identify new phosphatase substrates and adapters in growth pathways

et al. 2014

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Edited by:Protein phosphorylation homoeostasis is tightly controlled and pathological conditions are caused by subtle alterations of the cell phosphorylation profile. Altered levels of kinase activities have already been associated to specific diseases. Less is known about the impact of phosphatases, the enzymes that down-regulate phosphorylation by removing the phosphate groups. This is partly due to our poor understanding of the phosphatase-substrate network. Much of phosphatase substrate specificity is not based on intrinsic enzyme specificity with the catalytic pocket recognizing the sequence/structure context of the phosphorylated residue. In addition many phosphatase catalytic subunits do not form a stable complex with their substrates. This makes the inference and validation of phosphatase substrates a non-trivial task. Here, we present a novel approach that builds on the observation that much of phosphatase substrate selection is based on the network of physical interactions linking the phosphatase to the substrate. We first used affinity proteomics coupled to quantitative mass spectrometry to saturate the interactome of eight phosphatases whose down regulations was shown to affect the activation of the RAS-PI3K pathway. By integrating information from functional siRNA with protein interaction information, we develop a strategy that aims at inferring phosphatase physiological substrates. Graph analysis is used to identify protein scaffolds that may link the catalytic subunits to their substrates. By this approach we rediscover several previously described phosphatase substrate interactions and characterize two new protein scaffolds that promote the dephosphorylation of PTPN11 and ERK by DUSP18 and DUSP26, respectively.

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Section: Resultsmentioning

confidence: 99%

Combining affinity proteomics and network context to identify new phosphatase substrates and adapters in growth pathways

et al. 2014

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“…This strategy identified 28 overlapping targets, of which four overlapping candidate gene targets (DICER1, UBE4B, SGPP1, and PTPN21) were further analyzed based upon their potential involvement in radiation resistance or oncogenic processes (11,(25)(26)(27)(28). Using qRT-PCR, we verified that their expression were significantly decreased in PC3-miR-95 cells relative to PC3-control cells (Fig.…”

Section: Mir-95 Promotes Radiation Resistance Through Downregulation mentioning

confidence: 91%

miRNA-95 Mediates Radioresistance in Tumors by Targeting the Sphingolipid Phosphatase SGPP1

et al. 2013

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Radiation resistance poses a major clinical challenge in cancer treatment, but little is known about how microRNA (miR) may regulate this phenomenon. In this study, we used next-generation sequencing to perform an unbiased comparison of miR expression in PC3 prostate cancer cells rendered resistant to fractionated radiation treatment. One miR candidate found to be upregulated by ionizing radiation was miR-95, the enforced expression of which promoted radiation resistance in a variety of cancer cells. miR-95 overexpression recapitulated an aggressive phenotype including increased cellular proliferation, deregulated G 2 -M checkpoint following ionizing radiation, and increased invasive potential. Using combined in silico prediction and microarray expression analyses, we identified and validated the sphingolipid phosphatase SGPP1, an antagonist of sphingosine-1-phosphate signaling, as a target of miR-95 that promotes radiation resistance. Consistent with this finding, cell treatment with FTY720, a clinically approved small molecule inhibitor of S1P signaling, sensitized miR-95 overexpressing cells to radiation treatment. In vivo assays extended the significance of these results, showing that miR-95 overexpression increased tumor growth and resistance to radiation treatment in tumor xenografts. Furthermore, reduced tumor necrosis and increased cellular proliferation were seen after radiation treatment of miR-95 overexpressing tumors compared with control tumors. Finally, miR-95 expression was increased in human prostate and breast cancer specimens compared with normal tissue. Together, our work reveals miR-95 expression as a critical determinant of radiation resistance in cancer cells. Cancer Res; 73(23); 6972-86. Ó2013 AACR.

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“…PTPN21over-expression is thought to be an early step in urothelial cancer progression. In terms of expression in vivo, PTPN21 is absent from the normal bladder tissue, hyperplastic urothelium, and urothelial papilloma, whereas its expression gradually increases from low grade to high grade urothelial carcinoma (103).…”

Section: Renal Cell and Bladder Cancermentioning

confidence: 99%

The regulatory roles of phosphatases in cancer

et al. 2013

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The relevance of potentially reversible post-translational modifications required for controlling cellular processes in cancer is one of the most thriving arenas of cellular and molecular biology. Any alteration in the balanced equilibrium between kinases and phosphatases may result in development and progression of various diseases, including different types of cancer, though phosphatases are relatively under-studied. Loss of phosphatases such as PTEN (phosphatase and tensin homologue deleted on chromosome 10), a known tumour suppressor, across tumour types lends credence to the development of phosphatidylinositol 3 - kinase inhibitors alongside the use of phosphatase expression as a biomarker, though phase 3 trial data are lacking. In this review, we give an updated report on phosphatase dysregulation linked to organ-specific malignancies. © 2014 American Heart Association, Inc

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PTPD1 Supports Receptor Stability and Mitogenic Signaling in Bladder Cancer Cells

Cited by 49 publications

References 37 publications

Combining affinity proteomics and network context to identify new phosphatase substrates and adapters in growth pathways

Combining affinity proteomics and network context to identify new phosphatase substrates and adapters in growth pathways

miRNA-95 Mediates Radioresistance in Tumors by Targeting the Sphingolipid Phosphatase SGPP1

The regulatory roles of phosphatases in cancer

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