Engaged for survival

Geletu, Mulu; Guy, Stephanie; Arulanandam, Rozanne; Feracci, Hélène; Raptis, Leda

doi:10.4161/jkst.27363

Cited by 17 publications

(17 citation statements)

References 81 publications

(116 reference statements)

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“…Such nuclear effects appear to be cadherin-dependent, since even a purified E-cadherin ectodomain fragment elicits such responses (Arulanandam et al, 2009). Further, this relationship may be quite general among cadherins, as it has been observed for C- and M-cadherin (Charrasse et al, 2007; Noren, Niessen, Gumbiner, & Burridge, 2001), as well as N-cadherin and cadherin11 (Geletu et al, 2013). Under the conditions examined, IL6 production following cadherin-mediated homophilic ligation did not activate ERK1/2 (Arulanandam et al, 2009; Geletu et al, 2013; Raptis et al, 2000).…”

Section: Cadherin Nuclear Signaling By Small Gtpases and Nfκbmentioning

confidence: 68%

“…Further, this relationship may be quite general among cadherins, as it has been observed for C- and M-cadherin (Charrasse et al, 2007; Noren, Niessen, Gumbiner, & Burridge, 2001), as well as N-cadherin and cadherin11 (Geletu et al, 2013). Under the conditions examined, IL6 production following cadherin-mediated homophilic ligation did not activate ERK1/2 (Arulanandam et al, 2009; Geletu et al, 2013; Raptis et al, 2000). Thus, in the context of cadherin-mediated high cell densities, the STAT pathway appears to a major factor in conferring cell survival.…”

Section: Cadherin Nuclear Signaling By Small Gtpases and Nfκbmentioning

confidence: 68%

“…One relates to production of the IL6-cytokine, which binds cytokine receptors (e.g., gp130) on surrounding cells to initiate JAK-STAT signaling (Geletu et al, 2013). Cadherin ligation under high-density cell conditions, possibly mimicking cell-packing densities in vivo , affects Rho-family GTPase activity.…”

Section: Cadherin Nuclear Signaling By Small Gtpases and Nfκbmentioning

confidence: 99%

“…Related aspects of this topic have been addressed in a number of excellent reviews, to which the reader is directed (Cavallaro & Christofori, 2004; Cavallaro & Dejana, 2011; Daugherty & Gottardi, 2007; Gavard, 2013; Geletu, Guy, Arulanandam, Feracci, & Raptis, 2013; Heuberger & Birchmeier, 2010; McEwen, Escobar, & Gottardi, 2012; Nelson & Nusse, 2004; Paulson, Prasad, Thuringer, & Manzerra, 2014; Philippova et al, 2009; Stepniak, Radice, & Vasioukhin, 2009; Sun, Parrish, Hill, & Meininger, 2014; van Roy, 2014). In addition to providing a current analysis, we aim here to provide a perspective on cadherins that addresses a cross-section of the superfamily, especially in vertebrates.…”

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confidence: 99%

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Nuclear Signaling from Cadherin Adhesion Complexes

McCrea

Maher

Gottardi

2015

Current Topics in Developmental Biology

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The arrival of multicellularity in evolution facilitated cell–cell signaling in conjunction with adhesion. As the ectodomains of cadherins interact with each other directly in trans (as well as in cis), spanning the plasma membrane and associating with multiple other entities, cadherins enable the transduction of “outside-in” or “inside-out” signals. We focus this review on signals that originate from the larger family of cadherins that are inwardly directed to the nucleus, and thus have roles in gene control or nuclear structure–function. The nature of cadherin complexes varies considerably depending on the type of cadherin and its context, and we will address some of these variables for classical cadherins versus other family members. Substantial but still fragmentary progress has been made in understanding the signaling mediators used by varied cadherin complexes to coordinate the state of cell–cell adhesion with gene expression. Evidence that cadherin intracellular binding partners also localize to the nucleus is a major point of interest. In some models, catenins show reduced binding to cadherin cytoplasmic tails favoring their engagement in gene control. When bound, cadherins may serve as stoichiometric competitors of nuclear signals. Cadherins also directly or indirectly affect numerous signaling pathways (e.g., Wnt, receptor tyrosine kinase, Hippo, NFκB, and JAK/STAT), enabling cell–cell contacts to touch upon multiple biological outcomes in embryonic development and tissue homeostasis.

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Section: Cadherin Nuclear Signaling By Small Gtpases and Nfκbmentioning

confidence: 68%

Section: Cadherin Nuclear Signaling By Small Gtpases and Nfκbmentioning

confidence: 68%

Section: Cadherin Nuclear Signaling By Small Gtpases and Nfκbmentioning

confidence: 99%

mentioning

confidence: 99%

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Nuclear Signaling from Cadherin Adhesion Complexes

McCrea

Maher

Gottardi

2015

Current Topics in Developmental Biology

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“…STAT3 is activated following adheren junction formation 21 and STAT3 signaling has been implicated in gap junction intercellular communication, IL-6-induced vascular leakage, downregulation of VE-cadherin, and mir17–92/E2F1 dependent regulation of β-catenin nuclear translocation and transcriptional activity 22–28 . However, the specific role of STAT3 in endovascular permeability, in particular to mast cell mediators, has not previously been explored.…”

Section: Introductionmentioning

confidence: 99%

Diminution of signal transducer and activator of transcription 3 signaling inhibits vascular permeability and anaphylaxis

Hox

O’Connell

Lyons

et al. 2016

Journal of Allergy and Clinical Immunology

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Background During IgE-mediated immediate hypersensitivity reactions, vascular endothelial cells permeabilize in response to mast cell mediators. We have previously demonstrated that patients and mice with STAT3 mutations (autosomal dominant-hyper IgE syndrome; AD-HIES) are partially protected from anaphylaxis. Objectives To further study the mechanism by which STAT3 contributes to anaphylaxis, and determine whether small molecule inhibition of STAT3 can prevent anaphylaxis. Methods Using unaffected and STAT3-inhibited or genetic loss of function samples, we performed histamine skin prick testing, investigated the contribution of STAT3 to animal models of anaphylaxis, measured endothelial cell permeability, gene and protein expression, and histamine receptor-mediated signaling. Results While mouse mast cell degranulation was minimally affected by STAT3 blockade, mast cell mediator-induced anaphylaxis was blunted in Stat3 mutant AD-HIES mice and in wild-type mice subjected to small molecule STAT3 inhibition. Histamine skin prick responses were diminished in AD-HIES patients. Human umbilical vein vascular endothelial cells (HUVECs) derived from patients with AD-HIES or treated with a STAT3 inhibitor failed to properly signal through Src or to appropriately dissolute the adherens junctions made up of the proteins vascular endothelial (VE)-cadherin and β-catenin. Further, we found that diminished STAT3-target mir17–92 expression in AD-HIES HUVECS is associated with increased PTEN expression, which inhibits Src, and increased E2F1 expression, which regulates β-catenin cellular dynamics. Conclusions These data demonstrate that STAT3-dependent transcriptional activity regulates critical components for the architecture and functional dynamics of endothelial junctions thus permitting vascular permeability.

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STAT3 and metabolism: How many ways to use a single molecule?

Demaria

Camporeale

Poli

2014

Intl Journal of Cancer

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The transcription factor Signal Transducer and Activator of Transcription (STAT)3 has been considered as a potential anticancer target since its first description as an oncogene in 1999, recently leading to STAT3 inhibitors been brought to clinical trial for the treatment of solid tumors. However, the past 14 years of intense basic research have uncovered novel STAT3‐mediated pathways that could affect the outcome of the designed therapies while at the same time help designing function‐specific inhibitors. Particularly intriguing are the recent findings that suggest profound implications of STAT3 with the regulation of cellular metabolism in both canonical, that is transcriptional, and non‐canonical ways. Here, after a short description of the main known features of STAT3 signaling and function, we review the recent literature on the role of STAT3 in regulating cellular metabolism and discuss the potential consequences on the therapeutic approaches currently under clinical experimentation.

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Engaged for survival

Cited by 17 publications

References 81 publications

Nuclear Signaling from Cadherin Adhesion Complexes

Nuclear Signaling from Cadherin Adhesion Complexes

Diminution of signal transducer and activator of transcription 3 signaling inhibits vascular permeability and anaphylaxis

STAT3 and metabolism: How many ways to use a single molecule?

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