Jab1 is a target of EGFR signaling in ERα-negative breast cancer

Wang, Jiaxu; Barnes, Rebecca; West, N.; Olson, Melanie; Chu, Jenny E.; Watson, Peter H.

doi:10.1186/bcr2105

Cited by 35 publications

(36 citation statements)

References 44 publications

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“…We show that Psor was required for the pro-invasive activity of avb6 and that disruption of the association of Psor with the b6 cytoplasmic tail inhibited invasion of oral SCC cells. Previously avb6 and Psor have been implicated independently in carcinoma progression and invasion (Breuss et al, 1995;Clark et al, 1996;Haapasalmi et al, 1996;Larjava et al, 1996;Jones et al, 1997;Al-Haddad et al, 1999;Regezi et al, 2002;Jiang et al, 2004;Emberley et al, 2004;Krop et al, 2005;Banerjee et al, 2005;Ralhan et al, 2008;Wang et al, 2008;Paruchuri et al, 2008;Kesting et al, 2009), and our data identify a novel pro-invasive interaction that may explain some of these previous observations. The data further suggest that inhibition of this b6-Psor association may provide a novel therapeutic target to inhibit carcinoma invasion.…”

Section: Introductionsupporting

confidence: 72%

“…Interestingly, like avb6, psoriasin expression has been reported to be up-regulated in epithelial cells of various oral squamous carcinomas (Banerjee et al, 2005;Zhou et al, 2008;Ralhan et al, 2008;Kesting et al, 2009) and subsets of breast cancers (Al-Haddad et al, 1999;Jiang et al, 2004;Emberley et al, 2004Emberley et al, , 2005Krop et al, 2005;Petersson et al, 2007;Wang et al, 2008;Paruchuri et al, 2008). The precise role of Psor in tumour behaviour is, however, unclear.…”

Section: Discussionmentioning

confidence: 99%

“…As discussed below, this sometimes secreted protein has been implicated as promoting anti-microbial activity and inflammation (Glaser et al, 2005;Wolf et al, 2008), regulating cell survival and signalling (Emberley et al, 2005;Peterson et al, 2007;Zhou et al, 2008) and being upregulated in oral and breast cancer (Al-Haddad et al, 1999;Jiang et al, 2004;Emberley et al, 2004;Krop et al, 2005;Banerjee et al, 2005;Ralhan et al, 2008;Wang et al, 2008;Paruchuri et al, 2008;Kesting et al, 2009). We show that Psor was required for the pro-invasive activity of avb6 and that disruption of the association of Psor with the b6 cytoplasmic tail inhibited invasion of oral SCC cells.…”

Section: Introductionmentioning

confidence: 99%

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Psoriasin (S100A7) associates with integrin β6 subunit and is required for αvβ6-dependent carcinoma cell invasion

Morgan¹,

Jazayeri

Ramsay

et al. 2010

Oncogene

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Expression of the integrin avb6 is upregulated in a variety of carcinomas where it appears to be involved in malignant progression, although the biology of this integrin is not fully explored. We have generated oral carcinoma cells that express avb6 composed of wild-type av and a mutant b6 that lacks the unique C-terminal 11 amino acids (aa). We found that these residues, although not required for avb6-dependent adhesion or migration, are essential for avb6-dependent invasive activity. We have used a proteomic approach to identify novel binding partners for the b6 subunit cytoplasmic tail and report that psoriasin (Psor) (S100A7) bound preferentially to the recombinant b6 cytoplasmic domain, though not in the absence of the unique C-terminal 11aa. Endogenous cellular Psor coprecipitated with endogenous b6 and colocalised with avb6 at the cell membrane and intracellular vesicles. Knockdown of Psor, with small interfering RNA, had no effect on avb6-dependent adhesion or migration but abrogated avb6-mediated oral carcinoma cell invasion both in Transwell and, the more physiologically relevant, organotypic invasion assays, recapitulating the behaviour of the b6-mutant cell line. Membrane-permeant Tat-peptides encoding the unique C-terminal residues of b6, bound directly to recombinant Psor and inhibited cellular Psor binding to b6; this blocked avb6-dependent, but not avb6-independent, invasion. These data identify a novel interaction between Psor and b6 and demonstrate that it is required for avb6-dependent invasion by carcinoma cells. Inhibition of this interaction may represent a novel therapeutic strategy to target carcinoma invasion.

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Section: Introductionsupporting

confidence: 72%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Psoriasin (S100A7) associates with integrin β6 subunit and is required for αvβ6-dependent carcinoma cell invasion

Morgan¹,

Jazayeri

Ramsay

et al. 2010

Oncogene

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“…Although our data are preliminary this is intriguing, given previous observations that S100A7 itself may promote EGF expression and is involved in EGFR signaling (Emberley et al, 2005;Paruchuri et al, 2008;Wang et al, 2008). We have confirmed by analysis of expression levels in an independent breast tumor data set (UNC) that S100A7 correlates with EGFR expression in a large unselected cohort and within the ER-negative subset, supporting the existence of functional cooperativity between S100A7 and EGFR (Supplementary Table S2).…”

Section: Inflammatory Cytokines Induce S100a7 Expression In Breast Cellssupporting

confidence: 58%

“…Thus, activation of PI3K, ERK1/2 and STAT3 all appear to be necessary for full S100A7 induction by OSM or IL-6. We (Emberley et al, 2005;Wang et al, 2008) and others (Paruchuri et al, 2008) have previously shown a link between S100A7 and the epidermal growth factor (EGF) pathway. IL-6 and EGF signaling can also be functionally linked (Badache and Hynes, 2001).…”

Section: Inflammatory Cytokines Induce S100a7 Expression In Breast Cellsmentioning

confidence: 99%

S100A7 (psoriasin) is induced by the proinflammatory cytokines oncostatin-M and interleukin-6 in human breast cancer

West

Watson

2010

Oncogene

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S100A7 promotes aggressive features in breast cancer, although regulation of its expression is poorly understood. As S100A7 associates with inflammation in skin and breast tissue, we hypothesized that inflammatory cytokines may regulate S100A7 in breast cancer. We therefore examined the effects of several cytokines, among which oncostatin-M (OSM) and the related cytokine, interleukin (IL)-6, showed the most significant effects on S100A7 expression in breast tumor cells in vitro. Both cytokines consistently induced S100A7 expression in three cell lines (MCF7, T47D and MDA-MB-468) in a dose-and time-dependent manner. Induction of S100A7 was inhibited by blockade of STAT3, phosphatidylinositol 3 kinase (PI3K) and ERK1/2 signaling and small interference RNA (siRNA)-mediated knockdown of S100A7 eliminated the promigratory effects of OSM treatment. S100A7 mRNA levels in a case-control cohort of breast tumors (n ¼ 20) were significantly associated with expression of the OSM receptor b (OSMRb) chain (P ¼ 0.0098). This association was confirmed using publicly available microarray data from an independent breast tumor cohort (n ¼ 201, P ¼ 0.0005) and a correlation between S100A7 and poor patient survival was observed specifically in cases with high OSMRb expression (HR ¼ 2.35; P ¼ 0.0396; n ¼ 85). We conclude that inflammatory cytokines can regulate S100A7 expression and that S100A7 may mediate some of their effects in breast cancer.

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Bezielle (BZL101)‐induced oxidative stress damage followed by redistribution of metabolic fluxes in breast cancer cells: A combined proteomic and metabolomic study

Klawitter

Gurshtein

et al. 2011

Intl Journal of Cancer

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Bezielle (BZL101)-induced oxidative stress damage followed by redistribution of metabolic fluxes in breast cancer cells: a combined proteomic and metabolomic study Bezielle is an orally administered aqueous extract of Scutellaria barbata for treatment of advanced and metastatic breast cancer. Phase I trials showed promising tolerability and efficacy. In our study, we used a combined proteomic-metabolomic approach to investigate the molecular pathways affected by Bezielle in ER-positive BT474 and ER-negative SKBR3 cell lines. In both, Bezielle inhibited cell proliferation, induced cell death and G2 cycle arrest by regulating the mediator proteins Jab1, p27 Kip1 and p21 Cip1 . In addition, it stimulated reactive oxygen species production, hyperactivation of PARP and inhibition of glycolysis. Bezielle's ability to induce oxidative stress was associated with the changes in expression of redox potential maintaining enzymes: glutathione-and thioredoxin-related proteins and peroxiredoxins. In regards to cell metabolism, decreased expression of a-enolase was associated with a reduction of de novo 13 C-lactate formation. Reduced Krebs cycle activity as evidenced by the reduced expression of a-ketoglutarate dehydrogenase and succinyl-CoA synthetase led to decreased intracellular succinate concentrations. By inhibiting glucose metabolism, cells reacted by lowering the expression of glucose transporters and resulting in decreased intracellular glucose concentration. Decreased expression of fatty acid synthase and reduced concentration of phosphocholine indicated considerable changes in phospholipid metabolism. Ultimately, by inhibiting the major energy-producing pathways, Bezielle caused depletion of ATP and NAD(H). Both cell lines were responsive, thus suggesting that Bezielle has the potential to be effective against ER-negative breast cancers. In conclusion, Bezielle's cytotoxicity toward cancer cells is primarily based on inhibition of metabolic pathways that are preferentially activated in tumor cells thus explaining its specificity for cancer cells.

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Jab1 is a target of EGFR signaling in ERα-negative breast cancer

Cited by 35 publications

References 44 publications

Psoriasin (S100A7) associates with integrin β6 subunit and is required for αvβ6-dependent carcinoma cell invasion

Psoriasin (S100A7) associates with integrin β6 subunit and is required for αvβ6-dependent carcinoma cell invasion

S100A7 (psoriasin) is induced by the proinflammatory cytokines oncostatin-M and interleukin-6 in human breast cancer

Bezielle (BZL101)‐induced oxidative stress damage followed by redistribution of metabolic fluxes in breast cancer cells: A combined proteomic and metabolomic study

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