Tyrosine phosphatases as regulators of skeletal development and metabolism

Schiller, Katherine R.; Mauro, Laura J.

doi:10.1002/jcb.20515

Cited by 23 publications

(11 citation statements)

References 89 publications

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“…Furthermore, certain forms of PTPs have been shown to be a potential target for bisphosphate in the treatment of bone metastasis from cancer. Deregulation of these pathways has been implicated in cancer development and progression [4].…”

Section: Introductionmentioning

confidence: 99%

Protein Tyrosine Phosphatase µ (PTP µ or PTPRM), a Negative Regulator of Proliferation and Invasion of Breast Cancer Cells, Is Associated with Disease Prognosis

Park

Mason

et al. 2012

PLoS ONE

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BackgroundPTPRM has been shown to exhibit homophilic binding and confer cell-cell adhesion in cells including epithelial and cancer cells. The present study investigated the expression of PTPRM in breast cancer and the biological impact of PTPRM on breast cancer cells.DesignExpression of PTPRM protein and gene transcript was examined in a cohort of breast cancer patients. Knockdown of PTPRM in breast cancer cells was performed using a specific anti-PTPRM transgene. The impact of PTPRM knockdown on breast cancer was evaluated using in vitro cell models.ResultsA significant decrease of PTPRM transcripts was seen in poorly differentiated and moderately differentiated tumours compared with well differentiated tumours. Patients with lower expression of PTPRM had shorter survival compared with those which had a higher level of PTPRM expression. Knockdown of PTPRM increased proliferation, adhesion, invasion and migration of breast cancer cells. Furthermore, knockdown of PTPRM in MDA-MB-231 cells resulted in increased cell migration and invasion via regulation of the tyrosine phosphorylation of ERK and JNK.ConclusionsDecreased expression of PTPRM in breast cancer is correlated with poor prognosis and inversely correlated with disease free survival. PTPRM coordinated cell migration and invasion through the regulation of tyrosine phosphorylation of ERK and JNK.

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Section: Introductionmentioning

confidence: 99%

Protein Tyrosine Phosphatase µ (PTP µ or PTPRM), a Negative Regulator of Proliferation and Invasion of Breast Cancer Cells, Is Associated with Disease Prognosis

Park

Mason

et al. 2012

PLoS ONE

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“…Prominent, but by no means exclusive, examples include the ability of the non receptor-type phosphatase PTP1B to regulate glucose homeostasis and body mass, which affects signaling downstream of the insulin and leptin receptors, respectively [33][34][35][36][37][38]. The interested reader is referred to several recent reviews in this field [23,25,[39][40][41][42][43][44][45]. Studies such as these, coupled with recent success in pharmacological manipulation of tyrosine kinase activity in treating human disease, have suggested that inhibitors of specific PTPs may also be useful as pharmaceuticals, and have prompted attempts to develop such inhibitors (e.g.…”

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confidence: 98%

Protein tyrosine phosphatase epsilon and Neu-induced mammary tumorigenesis

Berman-Golan

Granot-Attas

Elson

2008

Cancer Metastasis Rev

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Aberrant regulation of the phosphorylation of proteins on tyrosine residues is a well-established cause of cancer. Protein tyrosine phosphatases (PTPs) share in the crucial function of maintaining appropriate levels of phosphorylation of cellular proteins, making them potentially key players in regulating the transformation process. The receptor-type tyrosine phosphatase Epsilon (RPTPepsilon) participates in supporting the transformed phenotype of mammary tumor cells induced in vivo by the Neu tyrosine kinase. The phosphatase is overexpressed in mammary tumors induced in mice by a Neu transgene and expression of RPTPepsilon in mouse mammary glands leads to massive hyperplasia and associated tumorigenesis. Furthermore, cells isolated from mammary tumors induced by Neu in mice genetically lacking RPTPepsilon appear less transformed and proliferate less well than corresponding mammary tumor cells isolated from mice expressing the phosphatase. At the molecular level, RPTPepsilon dephosphorylates and activates Src and the related kinases Yes and Fyn, and the activities of these kinases are significantly reduced in tumor cells lacking RPTPepsilon. Restoring the activities of these kinases reveals that it is only the reduced activity of Src that causes the aberrant morphology and proliferation rate of tumor cells lacking RPTPepsilon. RPTPepsilon is primed to activate Src, and presumably related kinases, following its phosphorylation by Neu at Y695 within its C-terminus. This event is crucial in enabling RPTPepsilon to activate Src, but appears not to affect the activity of RPTPepsilon towards unrelated substrates. We conclude that a Neu-RPTPepsilon-Src pathway exists in mouse mammary tumor cells, in which Neu phosphorylates RPTPepsilon thereby driving the phosphatase to specifically activate Src family kinases and to assist in maintaining the transformed phenotype.

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“…The tyrosine phosphorylation of cellular proteins is a critical signaling event in the regulation of all biological processes, including bone formation and resorption 33. The protein tyrosine kinases (PTKs), which catalyze the addition of a phosphate moiety, and the protein tyrosine phosphatases (PTPs), which remove that phosphate, are essential mediators of this type of signaling.…”

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confidence: 99%

Bone deposition, bone resorption, and osteosarcoma

Toledo

Oliveira

Okamoto

et al. 2010

Journal Orthopaedic Research

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Bone deposition and bone resorption are ongoing dynamic processes, constituting bone remodeling. Some bone tumors, such as osteosarcoma (OS), stimulate focal bone deposition. OS is the most common primary bone tumor in children and young adults. A complex network of genes regulates bone remodeling and alterations in its expression levels can influence the genesis and progression of bone diseases, including OS. We hypothesized that the expression profiles of bone remodeling regulator genes would be correlated with OS biology and clinical features. We used real-time PCR to evaluate the mRNA levels of the tartrate-resistant acid phosphatase (ACP5), colony stimulating factor-1 (CSF1R), bone morphogenetic protein 7 (BMP7), collagen, type XI, alpha 2 (COL11A2), and protein tyrosine phosphatases zeta 1 (PTPRZ1) genes, in 30 OS tumor samples and correlated with clinical and histological data. All genes analyzed, except CSF1R, were differentially expressed when compared with normal bone expression profiles. In our results, OS patients with high levels of COL11A2 mRNA showed worse overall (p ¼ 0.041) and event free survival (p ¼ 0.037). Also, a trend for better overall survival was observed in patients with samples showing higher expression of BMP7 (p ¼ 0.067). COL11A2 overexpression and BMP7 underexpression could collaborate to OS tumor growth, through its central role in bone remodeling process. ß

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Tyrosine phosphatases as regulators of skeletal development and metabolism

Cited by 23 publications

References 89 publications

Protein Tyrosine Phosphatase µ (PTP µ or PTPRM), a Negative Regulator of Proliferation and Invasion of Breast Cancer Cells, Is Associated with Disease Prognosis

Protein Tyrosine Phosphatase µ (PTP µ or PTPRM), a Negative Regulator of Proliferation and Invasion of Breast Cancer Cells, Is Associated with Disease Prognosis

Protein tyrosine phosphatase epsilon and Neu-induced mammary tumorigenesis

Bone deposition, bone resorption, and osteosarcoma

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