ZO-1 controls endothelial adherens junctions, cell–cell tension, angiogenesis, and barrier formation

Tornavaca, Olga; Chia, Minghao; Dufton, Neil; Almagro, Lourdes Osuna; Conway, Daniel E.; Randi, Anna M.; Schwartz, Martin A.; Matter, Karl; Balda, María S.

doi:10.1083/jcb.201404140

Cited by 448 publications

(419 citation statements)

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“…ZO-1 is a junctional adaptor protein that is essential for endothelial barrier formation; it regulates angiogenesis and is required for normal blood vessel formation. 21 AuNPs treatment increased the expression levels of ZO-1 (P,0.05; Figure 6D and F) and, thereby, maintained the integrity of endothelial junctions and reduced the probability for tumor cells to escape into circulation. Additionally, c-Myc is a nuclear phosphoprotein that influences cancer progression by promoting EMT or vascularization.…”

Section: Aunps Inhibit the Expression Of Mmp-2 And C-mycmentioning

confidence: 97%

Gold nanoparticles attenuate metastasis by tumor vasculature normalization and epithelial–mesenchymal transition inhibition

Li¹,

Li²,

Liu³

et al. 2017

IJN

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Angiogenesis is a process by which vessels are formed through preexisting ones, and this plays a key role in the progression of solid tumors. However, tumor vessels are influenced by excessive pro-angiogenic factors, resulting in deformed structures that facilitate the intravasation of tumor cells into the circulation and subsequent metastasis. Moreover, abnormal tumor vessels have low blood perfusion and thereby decreased oxygen infusion into tumors. This results in a hostile microenvironment that promotes epithelial–mesenchymal transition (EMT), a process in which epithelial cells lose their polarity and gain increased motility, which is associated with metastasis and invasion. Here, we demonstrate that gold nanoparticles (AuNPs) facilitate tumor vasculature normalization, increase blood perfusion and alleviate hypoxia in melanoma tumors. Additionally, AuNPs were observed to reverse EMT in tumors, accompanied by the alleviation of lung metastasis. These AuNPs inhibited the migration of B16F10 cells and reversed EMT in B16F10 cells, indicating that AuNPs could directly regulate EMT independent of improvements in hypoxia. Taken together, our data demonstrated that AuNPs could induce tumor vasculature normalization and reverse EMT, resulting in decreased melanoma tumor metastasis.

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Section: Aunps Inhibit the Expression Of Mmp-2 And C-mycmentioning

confidence: 97%

Gold nanoparticles attenuate metastasis by tumor vasculature normalization and epithelial–mesenchymal transition inhibition

Li¹,

Li²,

Liu³

et al. 2017

IJN

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“…This includes guanine nucleotide exchange factors (GEFs) for RhoA, p114RhoGEF/ ARHGEF18 and ARHGEF11, that are recruited to forming junctions by cingulin, JACOP, and ZO-1, respectively, to promote ROCK driven myosin activation and junction formation (Fig. 4A) [114][115][116] . Similarly, the Cdc42 GEF TUBA is recruited to tight junctions by ZO-1 and tricellulin and regulates the junctional actomyosin cytoskeleton 117,118 .…”

Section: Tight Junction Assemblymentioning

confidence: 99%

“…JAM-A stimulated Rap2 activation promotes stabilisation of adherens junctions; and activation of Rap1 affects adhesion to extracellular matrix and cell migration by regulating integrin β1 expression and recycling 156--159 . In endothelial cells, ZO-1 regulates overall cell-cell tension as well as tensile forces acting on adherens junctions by regulating recruitment of a complex formed by p114RhoGEF and JACOP, which stimulates junctional RhoA/ROCKII/myosin activation 116 . Loss of ZO-1 also promotes formation of stress fibres and focal adhesions indicating that signalling at tight junctions has cellwide consequences on the cytoskeleton and adhesion.…”

Section: Crosstalk With Other Adhesion Complexesmentioning

confidence: 99%

Tight junctions: from simple barriers to multifunctional molecular gates

Zihni

Mills

Matter

et al. 2016

Nat Rev Mol Cell Biol

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Main body of text: 5983 words 2Epithelia and endothelia separate different tissue compartments and protect multicellular organisms form the outside world. This requires the formation of tight junctions, selective gates that control paracellular diffusion of ions and solutes. Tight junctions also form the border between the apical and basolateral plasma membrane domains and are linked to the machinery that controls apicobasal polarization. Additionally, signalling networks that guide diverse cell behaviours and functions are connected to tight junctions, transmitting information to and from the cytoskeleton, nucleus and different cell adhesion complexes. Here, we discuss recent advances in our understanding of the molecular architecture and cellular functions of tight junctions.Microscopists in the 19 th century described the paracellular space between neighbouring cells within an epithelial sheet to be sealed by a "terminal bar", a structure later resolved by electron microscopy into a composite of distinct cell-cell junctions that is now called the epithelial junctional complex and is formed by tight junctions, adherens junctions and desmosomes 1,2 . As the former two junctions are more tightly associated and often reside at the apical end of the lateral membrane, they are often referred to as the apical junctional complex (however, in endothelia, tight junctions and adherens junctions can be intercalated) (Fig. 1). Tight junctions are essential for barrier formation, and their primary physiological role is to function as paracellular gates that restrict diffusion on the basis of size and charge. Selective paracellular diffusion is an essential process for the maintenance of homoeostasis in organs and tissues. Tight junctions have long been the most enigmatic of all adhesion complexes and eluded a detailed molecular and functional analysis due to their complex architecture. Recent years have witnessed the identification of a large array of components associated with tight junctions implicating these junctions in an unexpected range of different functions, thereby challenging the traditional model, in which tight junctions are considered a simple diffusion barrier formed by a rigid molecular complex. In line with these various functions, mutations in genes encoding tight junction proteins have been linked to a range of inherited human diseases. Additionally, tight junction components are known to be targeted by a number of pathogenic bacteria and viruses, which hijack tight junction proteins to enter and infect cells, or target junctional signalling mechanisms to cross tissue barriers. Although tight junctions are a vertebrate junction, many of their components and functions are evolutionarily conserved (Box 1).The main purpose of this review is to examine the recent advances in the unravelling of the molecular architecture of tight junctions and understanding their functions. We will discuss recent exciting insights into how tight junctions function as signalling platforms that guide cell behaviour and differen...

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“…ANGPTL4) in cells of the primary tumor. These cells are able to migrate through ECM, adhere to and invade brain vasculature, for example by downregulating the expression of cell-cell adhesion TJ molecules such as CLDN1 [57,58]. Once in the brain, angiogenesis promotion, endothelial proliferation and survival may have a higher priority rather than Oncotarget 75790 www.impactjournals.com/oncotarget characteristics such as adhesion and invasion.…”

Section: Discussionmentioning

confidence: 99%

Untitled

2017

Oncotarget

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ZO-1 controls endothelial adherens junctions, cell–cell tension, angiogenesis, and barrier formation

Abstract: ZO-1 regulates VE-cadherin–dependent endothelial junctions and actomyosin organization, thereby influencing cell–cell tension, migration, angiogenesis, and barrier formation

Cited by 448 publications

References 50 publications

Gold nanoparticles attenuate metastasis by tumor vasculature normalization and epithelial–mesenchymal transition inhibition

Gold nanoparticles attenuate metastasis by tumor vasculature normalization and epithelial–mesenchymal transition inhibition

Tight junctions: from simple barriers to multifunctional molecular gates

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ZO-1 controls endothelial adherens junctions, cell–cell tension, angiogenesis, and barrier formation

Abstract: ZO-1 regulates VE-cadherin–dependent endothelial junctions and actomyosin organization, thereby influencing cell–cell tension, migration, angiogenesis, and barrier formation

Cited by 448 publications

References 50 publications

Gold nanoparticles attenuate metastasis by tumor vasculature normalization and epithelial&ndash;mesenchymal transition inhibition

Gold nanoparticles attenuate metastasis by tumor vasculature normalization and epithelial&ndash;mesenchymal transition inhibition

Tight junctions: from simple barriers to multifunctional molecular gates

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Gold nanoparticles attenuate metastasis by tumor vasculature normalization and epithelial–mesenchymal transition inhibition

Gold nanoparticles attenuate metastasis by tumor vasculature normalization and epithelial–mesenchymal transition inhibition