Comparative analysis of the expression of ERBIN and Erb-B2 in normal human skin and cutaneous carcinomas.

Lebeau, Stéphanie; Masouyé, I.; Berti, Marina; Augsburger, Eric; Jh, Saurat; Borradori, Luca; Fontao, Lionel

doi:10.1111/j.1365-2133.2005.06687.x

Cited by 26 publications

(32 citation statements)

References 25 publications

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“…6,13,20,21 HER2 is regulated by many adaptor and scaffolding proteins; for instance erbin, which controls the receptor sorting. 7,11,22 The example being membranous expression in keratinocytes and upper suprabasal layer of normal skin, but cytoplasmic in basal layer. 22 In thyroid cancer, decreasing HER2 expression characterized dedifferentiated parts of poorly differentiated tumors up to immunonegativity in anaplastic carcinoma.…”

Section: Discussionmentioning

confidence: 99%

“…7,11,22 The example being membranous expression in keratinocytes and upper suprabasal layer of normal skin, but cytoplasmic in basal layer. 22 In thyroid cancer, decreasing HER2 expression characterized dedifferentiated parts of poorly differentiated tumors up to immunonegativity in anaplastic carcinoma. 17 In our study, we observed membranous-cytoplasmic HER2 labeling in normal adrenomedullary tissue, developing fetal autonomic neural crest cells and differentiating cells in neuroblastoma.…”

Section: Discussionmentioning

confidence: 99%

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Prognostic significance of HER2 expression in neuroblastic tumors

et al. 2010

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HER2 is essential for normal embryonic development and has a critical function in oncogenesis and progression of some types of cancer. Neuroblastic tumors create a heterogenous group of pediatric embryonal tumors of sympathoadrenal lineage. The biological and prognostic function of HER2 in these tumors is not well established. In this study, we evaluated the status of HER2, its prognostic significance, and clinicopathological correlations in series of 79 untreated neuroblastoma. The immunohistochemical assessment of HER2 and Ki-67 (proliferation index) as well as HER2 copy number status were performed on tissue microarrays. HER2 expression characterized 63 tumors, including 34 with low and 29 with high level, showing either membranous or mixed membranous-cytoplasmic pattern. Sixteen cases were HER2 immunonegative. The pattern of immunolabeling depended on the maturity of neuroblastic cells, being the most intense in differentiating neuroblasts. None of the tumors revealed HER2 amplification. In the examined group, 20% of patients died of disease from 4 to 107 months (median 18) from the diagnosis, and the survivors were followed up for 14-149 months (median 59). Patients' age, stage of disease, tumor location, mitosis/karyorrhexis index (MKI), and presence of HER2 expression were statistically significantly related to survival probability as detected by the Cox proportional hazard model. In the univariate analysis, Kaplan-Meier curves revealed significantly poorer outcome of HER2 negative than HER2-positive tumors (either low or high expression). The immunonegativity was associated with adverse clinicopathological parameters, including poor survival, metastatic stage of disease, un-or poorly differentiated histology, high MKI, and higher proliferation index. In conclusion, HER2 expression, not accompanied by gene amplification, is common in neuroblastic tumors. HER2 positivity seems to have a positive prognostic significance. HER2 expression with a variable pattern is a marker of the stage of neuroblastic cells differentiation.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Prognostic significance of HER2 expression in neuroblastic tumors

et al. 2010

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“…Based on earlier studies that localized Erbin to cell junctions in the suprabasal epidermis, we predicted that DSG1 and Erbin would colocalize in keratinocytes (20). Accordingly, by immunofluorescence, DSG1 and Erbin colocalized in both cultured keratinocytes expressing exogenous DSG1 and human plantar skin, indicating that functional complexes could potentially form under physiological conditions (Figure 2, A-D).…”

Section: Figurementioning

confidence: 99%

“…The screen identified a modulator of ERK signaling known to localize at epidermal cell borders in a differentiation-dependent manner named Erbin (also known as ERBB2IP) (19,20).…”

Section: Introductionmentioning

confidence: 99%

Desmoglein-1/Erbin interaction suppresses ERK activation to support epidermal differentiation

Harmon

Simpson²,

Johnson³

et al. 2013

J. Clin. Invest.

131

158

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Genetic disorders of the Ras/MAPK pathway, termed RASopathies, produce numerous abnormalities, including cutaneous keratodermas. The desmosomal cadherin, desmoglein-1 (DSG1), promotes keratinocyte differentiation by attenuating MAPK/ERK signaling and is linked to striate palmoplantar keratoderma (SPPK). This raises the possibility that cutaneous defects associated with SPPK and RASopathies share certain molecular faults. To identify intermediates responsible for executing the inhibition of ERK by DSG1, we conducted a yeast 2-hybrid screen. The screen revealed that Erbin (also known as ERBB2IP), a known ERK regulator, binds DSG1. Erbin silencing disrupted keratinocyte differentiation in culture, mimicking aspects of DSG1 deficiency. Furthermore, ERK inhibition and the induction of differentiation markers by DSG1 required both Erbin and DSG1 domains that participate in binding Erbin. Erbin blocks ERK signaling by interacting with and disrupting Ras-Raf scaffolds mediated by SHOC2, a protein genetically linked to the RASopathy, Noonan-like syndrome with loose anagen hair (NS/LAH). DSG1 overexpression enhanced this inhibitory function, increasing Erbin-SHOC2 interactions and decreasing Ras-SHOC2 interactions. Conversely, analysis of epidermis from DSG1-deficient patients with SPPK demonstrated increased Ras-SHOC2 colocalization and decreased Erbin-SHOC2 colocalization, offering a possible explanation for the observed epidermal defects. These findings suggest a mechanism by which DSG1 and Erbin cooperate to repress MAPK signaling and promote keratinocyte differentiation.

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“…We cannot rule out that there is also a minor colocalisation at the plasma membrane, as SARA has been shown to interact with TGFb receptors at the plasma membrane (Di Guglielmo et al, 2003) and ERBIN is also detected at the plasma membrane (Borg et al, 2000). Although the localisation of ERBIN on early endosomes has not been reported previously, individual ERBIN-positive cytosolic vesicles have been described, by immunohistochemistry, in basal cell carcinoma (BCC) (Lebeau et al, 2005), and punctate ERBIN staining has been observed, by immunofluorescence, in proximal dendrites (Calin-Jageman et al, 2007). Taken together, we define ERBIN as a newly identified SARA-interacting protein, which can colocalise with the latter on early endosomes.…”

Section: Discussionmentioning

confidence: 89%

ERBIN is a new SARA-interacting protein: competition between SARA and SMAD2 and SMAD3 for binding to ERBIN

Sflomos

Kostaras

Panopoulou

et al. 2011

Journal of Cell Science

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Summary SARA, an early endosomal protein, plays a key role in TGFb signalling, as it presents SMAD2 and SMAD3 for phosphorylation by the activated TGFb receptors. Here, we show that ERBIN is a new SARA-interacting protein that can be recruited by SARA to early endosomes. ERBIN was recently shown to bind and segregate phosphorylated SMAD2 and SMAD3 (SMAD2/3) in the cytoplasm, thereby inhibiting SMAD2/3-dependent transcription. SARA binds to ERBIN using a new domain, which we have called the ERBID (ERBIN-binding domain), whereas ERBIN binds to SARA using a domain (amino acids 1208-1265) that also interacts with SMAD2 and SMAD3, which we have called the SSID (SARA-and SMAD-interacting domain). We additionally show that SARA competes with SMAD2/3 for binding to ERBIN. In agreement, overexpression of SARA or the ERBID peptide reverses the inhibitory effect of ERBIN on SMAD2/3-dependent transcription. Taken together, these data suggest that the response of cells to TGFb and activin A can be influenced by the relative concentrations of SARA, ERBIN and SMAD2/3.

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Comparative analysis of the expression of ERBIN and Erb-B2 in normal human skin and cutaneous carcinomas.

Cited by 26 publications

References 25 publications

Prognostic significance of HER2 expression in neuroblastic tumors

Prognostic significance of HER2 expression in neuroblastic tumors

Desmoglein-1/Erbin interaction suppresses ERK activation to support epidermal differentiation

ERBIN is a new SARA-interacting protein: competition between SARA and SMAD2 and SMAD3 for binding to ERBIN

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