Expression of protein tyrosine phosphatase alpha (RPTPα) in human breast cancer correlates with low tumor grade, and inhibits tumor cell growth in vitro and in vivo

Ardini, Elena; Agresti, Roberto; Tagliabue, Elda; Greco, Marco; Aiello, Piera; Yang, Liang-Tung; Ménard, Sylvie; Sap, Jan

doi:10.1038/sj.onc.1203869

Cited by 70 publications

(64 citation statements)

References 62 publications

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“…Tyrosine phosphorylation is also determined by protein tyrosine phosphatases (PTP), which can counterbalance actions of PTKs and act as mediators of cellular adhesion, leading to the hypothesis that some PTP genes might constitute tumor suppressor genes (Hunter, 1989;Beltran and Bixby, 2003). Supporting this hypothesis it has been shown that the expression of PTP in breast tumor cells induced delayed tumor growth and metastasis (Ardini et al, 2000). A member of the transmembrane tyrosine phosphatase family LAR-PTP (leukocyte common antigen-related protein-tyrosine phosphatase) is associated with the E-cadherin/␤-catenin complex (Kypta et al, 1996).…”

Section: Introductionmentioning

confidence: 67%

Targets of Fibroblast Growth Factor 1 (FGF-1) and FGF-2 Signaling Involved in the Invasive and Tumorigenic Behavior of Carcinoma Cells

Billottet

Elkhatib

Thiery

et al. 2004

MBoC

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Fibroblast growth factor (FGF)-1 and -2 have potent biological activities implicated in malignant tumor development. Their autocrine and nonautocrine activity in tumor progression of carcinoma was investigated in the NBT-II cell system. Cells were manipulated to either produce and be autocrine for FGF-1 or -2 or to only produce but not respond to these factors. The autocrine cells are highly invasive and tumorigenic and the determination of specific targets of FGF/fibroblast growth factor receptor (FGFR) signaling was assessed. In vitro studies showed that nonautocrine cells behave like epithelial parental cells, whereas autocrine cells have a mesenchymal phenotype correlated with the overexpression of urokinase plasminogen activator receptor (uPAR), the internalization of E-cadherin, and the redistribution of ␤-catenin from the cell surface to the cytoplasm and nucleus. uPAR was defined as an early target, whereas E-cadherin and the leukocyte common antigen-related protein-tyrosine phosphatase (LAR-PTP) were later targets of FGF signaling, with FGFR1 activation more efficient than FGFR2 at modulating these targets. Behavior of autocrine cells was consistent with a decrease of tumor-suppressive activities of both E-cadherin and LAR-PTP. These molecular analyses show that the potential of these two growth factors in tumor progression is highly dependent on specific FGFR signaling and highlights its importance as a target for antitumor therapy

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Section: Introductionmentioning

confidence: 67%

Targets of Fibroblast Growth Factor 1 (FGF-1) and FGF-2 Signaling Involved in the Invasive and Tumorigenic Behavior of Carcinoma Cells

Billottet

Elkhatib

Thiery

et al. 2004

MBoC

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“…This model suggests that cells expressing high levels of RPTPa, such as colon cancer cells, are able to overcome limitations of signal intensity (matrix force) by increased receptor levels. Although it has been shown that expression of RPTPa correlates with low tumor grade in breast cancers (Ardini et al, 2000), there are several reports that support a pro-malignant function of RPTPa. Overexpression of RPTPa is observed in advanced colon carcinoma (Tabiti et al, 1995) and expression of RPTPa correlates with gastric cancer progression including lymphovascular invasion and peritoneal dissemination (Wu et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

Substrate stiffness and the receptor-type tyrosine-protein phosphatase alpha regulate spreading of colon cancer cells through cytoskeletal contractility

et al. 2010

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Microenvironmental clues are critical to cell behavior. One of the key elements of migration is the generation and response to forces. Up to now, there is no definitive concept on how the generation and responses to cellular forces influence cancer-cell behavior. Here, we show that expression of receptor-type tyrosine-protein phosphatase alpha (RPTPa) in human SW480 colon cancer cells sets a threshold for the response to matrix forces by changing cellular contractility. This can be explained as an RPTPamediated increase in contractility with a consecutive increase in number and size of adhesion sites and stress fibers. These effects are mediated through myosin light chain kinase and largely independent of Rho/Rho-kinase (ROCK) signaling. In addition, we report that RPTPa influences spreading on low-rigidity surfaces, binding of collagen-coated beads and expression of RPTPa is required for invasion into the chorioallantoic membrane. These data suggest that force-responsive proteins such as RPTPa can influence cancer-cell behavior and identify potential targets for cancer therapy.

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“…Effectively, the role of these enzymes in cancer is poorly understood. Keane et al (18) demonstrate by inducible transfection that DEP-1 had an antiproliferative effect in MCF7 cells, and Ardini et al (42) show a positive correlation between high expression of PTP ␣ and delayed tumor growth and metastasis. Only SHP-1 was clearly implicated in the apoptotic process in breast cancer; the membrane recruitment of this enzyme by the somatostatin receptor or Fas has been shown to be an early event in their signaling that induced intracellular acidificationdependent apoptosis (17).…”

Section: Ptpl1/fap-1 Apoptotic Effect Is Independent Of the Fasmentioning

confidence: 99%

Protein-tyrosine Phosphatase PTPL1/FAP-1 Triggers Apoptosis in Human Breast Cancer Cells

Bompard¹,

Puech

Prébois

et al. 2002

Journal of Biological Chemistry

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Studies in Jurkat leukemia cells have suggested that protein-tyrosine phosphatase PTPL1/FAP-1 rescues Fasinduced cell death. However, we have previously shown that this enzyme triggers 4-hydroxytamoxifen-induced growth inhibition in human breast cancer cells. The present study addresses the role of PTPL1/FAP-1 in antiestrogen-regulated apoptotic effect and insulin-like growth factor-I survival action in MCF7 cells and further identifies the impacted signaling pathway. By terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling and cytoplasmic nucleosome enzyme-linked immunosorbent assay, we demonstrated that 4-hydroxytamoxifen-induced apoptosis was totally lost in PTPL1/FAP-1 antisense transfectants in which enzyme expression was abrogated, revealing the crucial role of this phosphatase in the apoptotic process in human breast cancer cells. Time-dependent expression of PTPL1/FAP-1 in MCF7 cells completely abolished the survival action of insulin-like growth factor-I. This effect occurred through a highly significant reduction in phosphatidylinositol 3-kinase/Akt pathway activation (80% reduction in phosphatidylinositol 3-kinase activity, 55% inhibition of Akt activation) accompanied by a 65% decrease in insulin receptor substrate-1 growth factor-induced tyrosine phosphorylation. These results provide the first evidence that PTPL1/FAP-1 has a key role in the apoptotic process in human breast cancer cells independent of Fas but associated with an early inhibition of the insulin receptor substrate-1/phosphatidylinositol 3-kinase pathway. Our data therefore suggest new therapeutic routes and strengthen the importance of identifying endogenous regulators and substrates of this phosphatase in breast tumors.Breast cancer is one of the most common malignancies affecting women in the Western countries. Although mortality and survival rates decreased in the UK (1), breast cancer incidence is still increasing. It is therefore crucial in the coming years to design new therapeutic strategies based on the updated knowledge of the mechanisms by which tumor growth is sustained.Breast cancer proliferation is the result of the balance between cell division and cell apoptosis. It has been shown in vitro in human breast cancer cell models that steroid hormones (mostly estrogens) and growth factors (epidermal growth factor, transforming growth factor ␣, IGF-I 1 and II, etc.) are the major signals affecting proliferation (2, 3). Most of these factors stimulate cell division and/or promote cell survival by mechanisms yet poorly understood, thus conferring growth advantage to tumor-responsive cells. On the other side, growth inhibitors and various antagonists have been shown to increase breast cancer cell apoptosis (4, 5).Estrogens and their antagonists mediate their action through their nuclear receptors (estrogen receptors ␣ and ␤), acting as transcriptional factors in coordination with numerous additional transcriptional cofactors. Peptide hormones and growth factor-signaling pathways involve the activation of sev...

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Expression of protein tyrosine phosphatase alpha (RPTPα) in human breast cancer correlates with low tumor grade, and inhibits tumor cell growth in vitro and in vivo

Cited by 70 publications

References 62 publications

Targets of Fibroblast Growth Factor 1 (FGF-1) and FGF-2 Signaling Involved in the Invasive and Tumorigenic Behavior of Carcinoma Cells

Targets of Fibroblast Growth Factor 1 (FGF-1) and FGF-2 Signaling Involved in the Invasive and Tumorigenic Behavior of Carcinoma Cells

Substrate stiffness and the receptor-type tyrosine-protein phosphatase alpha regulate spreading of colon cancer cells through cytoskeletal contractility

Protein-tyrosine Phosphatase PTPL1/FAP-1 Triggers Apoptosis in Human Breast Cancer Cells

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