The transmembrane protein tyrosine phosphatase RPTPσ modulates signaling of the epidermal growth factor receptor in A431 cells

E, Suárez Pestana; Tenev, Tencho; Gross, Steffen; Stoyanov, Borislav; Ogata, Masato; Fd, Böhmer

doi:10.1038/sj.onc.1202794

Cited by 71 publications

(17 citation statements)

References 52 publications

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“…This observation further supports the concept that EGFR is acted upon by multiple RPTPs. In this regard, both RPTP LAR, and RPTP-have been shown to reduce EGFR phosphorylation (18,23). However, whether either RPTP acts directly on EGFR, or which phosphotyrosine residue(s) either RPTP affects remains to be determined.…”

Section: Discussionmentioning

confidence: 99%

Receptor-type Protein-tyrosine Phosphatase-κ Regulates Epidermal Growth Factor Receptor Function

Tan

Grachtchouk

et al. 2005

Journal of Biological Chemistry

106

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Epidermal growth factor receptor (EGFR), the prototypic receptor protein tyrosine kinase, is a major regulator of growth and survival for many epithelial cell types. We report here that receptortype protein-tyrosine phosphatase-(RPTP-) dephosphorylates EGFR and thereby regulates its function in human keratinocytes. Protein-tyrosine phosphatase (PTP) inhibitors induced EGFR tyrosine phosphorylation in intact primary human keratinocytes and cell-free membrane preparations. Five highly expressed RPTPs (RPTP-␤, ␦, , , and ) were functionally analyzed in a Chinese hamster ovary (CHO) cell-based expression system. Full-length human EGFR expressed in CHO cells, which lack endogenous EGFR, displayed high basal (i.e. in the absence of ligand) tyrosine phosphorylation. Co-expression of RPTP-, but not other RPTPs, specifically reduced basal EGFR tyrosine phosphorylation. RPTPalso reduced epidermal growth factor-dependent EGFR tyrosine phosphorylation in CHO cells. Purified RPTP-preferentially dephosphorylated EGFR tyrosines 1068 and 1173 in vitro. Overexpression of wild-type or catalytically inactive RPTP-reduced or enhanced, respectively, basal and EGF-induced EGFR tyrosine phosphorylation in human keratinocytes. Furthermore, siRNA-mediated knockdown of RPTP-increased basal and EGF-stimulated EGFR tyrosine phosphorylation and augmented downstream Erk activation in human keratinocytes. RPTP-levels increased in keratinocytes as cells reached confluency, and overexpression of RPTP-in subconfluent keratinocytes reduced keratinocyte proliferation. Taken together, the above data indicate that RPTP-is a key regulator of EGFR tyrosine phosphorylation and function in human keratinocytes.

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Section: Discussionmentioning

confidence: 99%

Receptor-type Protein-tyrosine Phosphatase-κ Regulates Epidermal Growth Factor Receptor Function

Tan

Grachtchouk

et al. 2005

Journal of Biological Chemistry

106

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“…To the best of our knowledge, focal somatic alteration of this gene has not been described in human disease. PTPRS has been shown to directly interact with and dephosphorylate EGFR (34,35). We observed deletions in this gene that were highly focal, robustly identifying PTPRS as the target of CNA on chromosome 19p13.3, a genomic region frequently lost in several cancers and thought to harbor an as-yet-unidentified tumor suppressor (36)(37)(38)(39).…”

Section: Protein Tyrosine Phosphatase Receptor S (Ptprs) Is Frequentlymentioning

confidence: 99%

“…Alterations of PTPRS in cancer are poorly described, and no focal alterations of this gene have been documented. Biochemical experiments have demonstrated that PTPRS directly interacts with EGFR and dephosphorylates and inactivates EGFR and loss of PTPRS enhances EGFR-induced transformation (34,35). The microdeletions in PTPRS result in loss of mRNA expression (Fig.…”

Section: Protein Tyrosine Phosphatase Receptor S (Ptprs) Is Frequentlymentioning

confidence: 99%

Genomic dissection of the epidermal growth factor receptor (EGFR)/PI3K pathway reveals frequent deletion of the EGFR phosphatase PTPRS in head and neck cancers

Morris¹,

Taylor²,

Bivona³

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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Activation of the PI3K and epidermal growth factor receptor (EGFR) pathway is able to drive oncogenesis in multiple human cancers, including head and neck squamous cell carcinoma. Targeted agents such as cetuximab and erlotinib are currently used in patients with head and neck squamous cell carcinoma, but, in this disease, the genomic alterations that cause pathway activation and determine response to pharmacologic inhibition remain ill-defined. Here, we present a detailed dissection of the EGFR/PI3K pathway, composed of sequencing of the core pathway components, and high-resolution genomic copy number assessment. Mutations were found in PIK3CA (6%), but no point mutations were observed in other pathway genes such as PTEN and EGFR . In contrast, we observed frequent copy number alterations of genes in the pathway, including PIK3CA , EGFR , protein tyrosine phosphatase receptor S ( PTPRS ), and RICTOR . In total, activating genetic pathway alterations were identified in 74% of head and neck tumors. Importantly, intragenic microdeletions of the EGFR phosphatase PTPRS were frequent (26%), identifying this gene as a target of 19p13 loss. PTPRS loss promoted EGFR/PI3K pathway activation, modulated resistance to EGFR inhibition, and strongly determined survival in lung cancer patients with activating EGFR mutations. These findings have important implications for our understanding of head and neck cancer tumorigenesis and for the use of targeted agents for this malignancy.

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“…Pestana et al 31 reported that EGF receptor dephosphorylation was activated by GM3 and that this event was mediated by the activation of receptor-type protein tyrosine phosphatase by GM3. Hence, GD1a is likely to activate the protein tyrosine phosphatases (hypothesis iv).…”

Section: Level Of C-met Tyrosine Phosphorylation In Gd1a-pretreated Hmentioning

confidence: 99%

Ganglioside GD1a inhibits HGF-induced motility and scattering of cancer cells through suppression of tyrosine phosphorylation of c-Met

Hyuga¹,

Kawasaki²,

Hyuga³

et al. 2001

Int. J. Cancer

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We previously reported that ganglioside GD1a, which is highly expressed in poorly metastatic FBJ-S1 cells, inhibits the serum-induced motility of FBJ-LL cells and that the metastatic potential of FBJ-LL cells is completely suppressed by enforced GD1a expression (Hyuga et al., Int J Cancer 1999; 83:685-91). We recently discovered that hepatocyte growth factor (HGF) induces FBJ-LL cell motility. In the present study, the HGF-induced motility of FBJ-S1 cells was found to be one-thirtieth that of FBJ-LL cells. This motility of GD1a-expressing transfectants, which were produced by transfection of FBJ-LL cells with GM2/GD2 synthase cDNA, decreased with increases in their GD1a expression and HGF induced almost no motility in GD1a-pretreated FBJ-LL cells, indicating that GD1a inhibits the HGF-induced motility of GD1a; HGF; motility; scattering Gangliosides are sialylated glycosphingolipids found on the outer layer of the plasma membrane. Changes in ganglioside expression in cancer cells are strongly related to their metastatic potential. 1-5 Although increases in complex ganglioside expression in cancer cells have been considered to be associated with malignancy, in our previous study we found that the poorly metastatic FBJ-S1 cells highly expressed the complex ganglioside GD1a, whereas the highly metastatic FBJ-LL cells only slightly expressed this ganglioside. 6 GD1a inhibited the serum-induced motility of FBJ-LL cells and the metastatic potential of FBJ-LL cells was completely suppressed by enforced GD1a expression. 7 It is possible that GD1a suppresses metastasis of FBJ-LL cells by inhibiting cell migration. The target molecules of GD1a need to be identified to clarify the mechanism of inhibition of metastasis by GD1a. Key words:We recently found that HGF induces FBJ-LL cell motility 8 and that the serum-induced motility of FBJ-LL cells was decreased by treatment of the serum with anti-HGF antibody (unpublished data), suggesting that HGF is a migration-stimulating factor in serum. Since FBJ-LL cells metastasize to the liver and HGF is secreted by nonparenchymal liver cells, HGF may promote liver metastasis of FBJ-LL cells. We suspect that HGF may play a key role in FBJ-LL cell metastasis. HGF is a multipotential modulator of biologic activities in a variety of cell types and it influences the growth, motility, differentiation and morphogenesis of its target cells through the c-Met tyrosine kinase receptor. 9 HGF has been described as a potent chemotactic factor 10 and has been associated with the progression of carcinoma cells. 11 Overexpression of the HGF receptor, c-Met, in malignant cells has been reported in various tissues. 12 Hence HGF may play a crucial role in cancer metastasis.In the present study, we attempted to identify the target molecules of GD1a by analyzing the molecular mechanism of the inhibition of cell migration by GD1a. We found that GD1a inhibited the HGFinduced motility, morphologic change and formation of actin stress fibers in FBJ-LL cells through suppression of tyrosine phosphorylation ...

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The transmembrane protein tyrosine phosphatase RPTPσ modulates signaling of the epidermal growth factor receptor in A431 cells

Cited by 71 publications

References 52 publications

Receptor-type Protein-tyrosine Phosphatase-κ Regulates Epidermal Growth Factor Receptor Function

Receptor-type Protein-tyrosine Phosphatase-κ Regulates Epidermal Growth Factor Receptor Function

Genomic dissection of the epidermal growth factor receptor (EGFR)/PI3K pathway reveals frequent deletion of the EGFR phosphatase PTPRS in head and neck cancers

Ganglioside GD1a inhibits HGF-induced motility and scattering of cancer cells through suppression of tyrosine phosphorylation of c-Met

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