Abstract:
:The ability of blood vessels to sense and respond to stimuli such as fluid flow, shear stress, and trafficking of immune cells is critical to the proper function of the vascular system. Endothelial cells constantly remodel their cell-cell junctions and the underlying cytoskeletal network in response to these exogenous signals. This remodeling, which depends on regulation of the linkage between actin and integral junction proteins, is controlled by a complex signaling network consisting of small G proteins and their various downstream effectors. In this commentary, we summarize recent developments in understanding the small G protein RAP1 and its effector RASIP1 as critical mediators of endothelial junction stabilization, and the relationship between RAP1 effectors and modulation of different subsets of endothelial junctions. The vasculature is a dynamic organ that is constantly exposed to a variety of signaling stimuli and mechanical stresses. In embryogenesis, nascent blood vessels form via a process termed vasculogenesis, wherein mesodermally derived endothelial precursor cells aggregate into cords, which subsequently form a lumen that permits trafficking of plasma and erythrocytes. (1)(,) (2) Angiogenesis occurs after establishment of this primitive vascular network, where new vessels sprout from existing vessels, migrate into newly expanded tissues, and anastomose to form a functional and complex circulatory network. (1)(,) (2) In the mouse, this process occurs through the second half of embryogenesis and into postnatal development in some tissues, such as the developing retinal vasculature. (3) Further, angiogenesis occurs in a variety of pathological conditions, such as diabetic retinopathy, age-related macular degeneration, inflammatory diseases such as rheumatoid arthritis, wound healing, and tumor growth. (1)(,) (2)(,) (4) Both vasculogenesis and angiogenesis are driven through signaling by vascular endothelial growth factor (VEGF), and therapeutic agents targeting this pathway have shown efficacy in a number of diseases. (5)(-) (9) Blood vessels must have a sufficient degree of integrity so as to not allow indiscriminate leak of plasma proteins and blood cells into the underlying tissue. However, vessels must be able to sense their environment, respond to local conditions, and mediate the regulated passage of protein, fluid, and cells. For example, endothelial cells are the primary point of attachment for immune cells leaving the blood stream and entering tissue, and leukocytes subsequently migrate either through the endothelial cell body itself (the transcellular route), or through transient disassembly of cell-cell junctions (the paracellular route). (10) Precise regulation of endothelial junctions is critical to the proper maintenance of vascular integrity and related processes, and disruption of vascular cell-cell contacts is an underlying cause or contributor to numerous pathologies such as cerebral cavernous malformations (CCM) and hereditary hemorrhagic telangiectasia (HHT). (11)(-) (13) Understanding the basic mechanisms of endothelial junction formation and maintenance will therefore lead to a greater chance of success of therapeutic intervention in these pathologic conditions, especially in instances where targeting of VEGF signaling is insufficient to resolve vascular abnormalities.
journal_name
Cell Adh Migrjournal_title
Cell adhesion & migrationauthors
Wilson CW,Ye Wdoi
10.4161/cam.28115subject
Has Abstractpub_date
2014-01-01 00:00:00pages
76-83issue
2eissn
1933-6918issn
1933-6926pii
28115journal_volume
8pub_type
杂志文章abstract::Visceral adipose tissue (VAT) may play a critical role in atherosclerotic cardiovascular disease. The goal of this study was to determine the effect of human VAT-released pro‑inflammatory cytokines on monocyte adhesion to the endothelium. The cytokine effects on monocyte adhesion to the endothelial cells (ECs) were te...
journal_title:Cell adhesion & migration
pub_type: 杂志文章
doi:10.1080/19336918.2019.1644856
更新日期:2019-12-01 00:00:00
abstract::The mechanical and structural properties of the extracellular matrix (ECM) play an important role in regulating cell fate. The natural ECM has a complex fibrillar structure and shows nonlinear mechanical properties, which are both difficult to mimic synthetically. Therefore, systematically testing the influence of ECM...
journal_title:Cell adhesion & migration
pub_type: 杂志文章
doi:10.1080/19336918.2016.1151607
更新日期:2016-09-02 00:00:00
abstract::Growth factors regulate a diverse array of cellular functions including proliferation, survival, movement, and the ability to do this often involves interactions with the extracellular matrix (ECM) and particularly heparan sulfate proteoglycans (HSPGs). HSPGs have been shown to sequester growth factors, and to act as ...
journal_title:Cell adhesion & migration
pub_type: 杂志文章
doi:10.4161/cam.4.4.12427
更新日期:2010-10-01 00:00:00
abstract::The actin cytoskeleton plays a key role in regulating cell motility. Caldesmon (CaD) is an actin-linked regulatory protein found in smooth muscle and non-muscle cells that is conserved among a variety of vertebrates. It binds and stabilizes actin filaments, as well as regulating actin-myosin interaction in a calcium (...
journal_title:Cell adhesion & migration
pub_type: 杂志文章,评审
doi:10.4161/cam.5.2.14398
更新日期:2011-03-01 00:00:00
abstract::Mitogen-activated protein kinases (MAPK) are among the major widespread transduction pathways in humans. They are involved in several inflammatory disorders, including the pathogenesis of inflammatory bowel disease (IBD). A recent paper showed that activated MAPK are upregulated on endothelium and fibroblasts from int...
journal_title:Cell adhesion & migration
pub_type: 杂志文章
doi:10.4161/cam.3.3.9152
更新日期:2009-07-01 00:00:00
abstract::Trophoblast migration and invasion through the decidua and maternal uterine spiral arteries are crucial events in placentation. During this process, invasive trophoblast replace vascular endothelial cells as the uterine arteries are remodeled to form more permissive vessels that facilitate adequate blood flow to the g...
journal_title:Cell adhesion & migration
pub_type: 杂志文章,评审
doi:10.1080/19336918.2015.1120397
更新日期:2016-03-03 00:00:00
abstract::Familial dysautonomia (FD) is a hereditary neuronal disease characterized by poor development and progressive degeneration of the sensory and autonomic nervous system. Majority of FD (99.5%) results from a single nucleotide point mutation in the IKBKAP gene encoding IKAP, also known as elongation protein 1 (ELP1). The...
journal_title:Cell adhesion & migration
pub_type: 杂志文章
doi:10.4161/cam.2.4.6630
更新日期:2008-10-01 00:00:00
abstract::There is currently great interest in the use of mesenchymal stem cells as a therapy for multiple sclerosis with potential to both ameliorate inflammatory processes as well as improve regeneration and repair. Although most clinical studies have used autologous bone marrow-derived mesenchymal stem cells, other sources s...
journal_title:Cell adhesion & migration
pub_type: 杂志文章
doi:10.4161/cam.26941
更新日期:2013-09-01 00:00:00
abstract::The hypotheses emerging from basic research on colorectal liver metastases must be tested in clinical situations for the adaptation of current treatment strategies. Pre-metastatic niches have been shown to exist in human colorectal synchronous metastases, with the liver parenchyma adjacent to the synchronous liver met...
journal_title:Cell adhesion & migration
pub_type: 杂志文章,评审
doi:10.4161/cam.23247
更新日期:2012-11-01 00:00:00
abstract::A deterministic model of dermal wound invasion, which accounts for the platelet-derived growth factor (PDGF) gradient sensing mechanism in fibroblasts mediated by cell surface receptors and the phosphoinositide 3-kinase (PI3K) signal transduction pathway, was previously described (Biophys J 2006; 90:2297-308). Here, w...
journal_title:Cell adhesion & migration
pub_type: 杂志文章
doi:10.4161/cam.2.2.6511
更新日期:2008-04-01 00:00:00
abstract::Orderly cell migration is essential for embryonic development, efficient wound healing and a functioning immune system and the dysregulation of this process leads to a number of pathologies. The speed and direction of cell migration is critically dependent on the structural organization of focal adhesions in the cell....
journal_title:Cell adhesion & migration
pub_type: 杂志文章
doi:10.4161/cam.4.2.10888
更新日期:2010-04-01 00:00:00
abstract::Cell surface receptors of the integrin family are pivotal to cell adhesion and migration. The activation state of heterodimeric alphabeta integrins is correlated to the association state of the single-pass alpha and beta transmembrane domains. The association of integrin alphaIIbbeta3 transmembrane domains, resulting ...
journal_title:Cell adhesion & migration
pub_type: 杂志文章
doi:10.4161/cam.4.2.10592
更新日期:2010-04-01 00:00:00
abstract::In this review, we summarized data on the formation and structure of the long and highly adhesive membrane tubulovesicular extensions (TVEs, membrane tethers or cytonemes) observed in human neutrophils and other mammalian cells, protozoan parasites and bacteria. We determined that TVEs are membrane protrusions charact...
journal_title:Cell adhesion & migration
pub_type: 杂志文章,评审
doi:10.4161/cam.23130
更新日期:2013-03-01 00:00:00
abstract::ARHI is an imprinted tumor suppressor gene that is downregulated in > 60% of ovarian cancers, associated with decreased progression-free survival. ARHI encodes a 26 kDa GTPase with homology to Ras. Re-expression of ARHI inhibits ovarian cancer growth, initiates autophagy and induces tumor dormancy. Recent studies have...
journal_title:Cell adhesion & migration
pub_type: 评论,杂志文章
doi:10.4161/cam.23648
更新日期:2013-03-01 00:00:00
abstract::Anti-angiogenic vascular endothelial growth factor A (VEGF) 165b and pro-angiogenic VEGF 165 are generated from the same transcript, and their relative amounts are dependent on alternative splicing. The role of VEGF 165b has not been investigated in as much detail as VEGF 165, although it appears to be highly expresse...
journal_title:Cell adhesion & migration
pub_type: 杂志文章,评审
doi:10.4161/cam.22439
更新日期:2012-11-01 00:00:00
abstract::Discovered decades ago, extracellular vesicles (EVs) emerge as dedicated organelles, able to deliver protected, specific cellular cues throughout the organism. While virtually every cell can release EVs, cancer cells co-opted this feature and efficiently unleashed them both in the tumor microenvironment and toward hea...
journal_title:Cell adhesion & migration
pub_type: 杂志文章,评审
doi:10.1080/19336918.2016.1247145
更新日期:2017-03-04 00:00:00
abstract::During development, dorsal root ganglion (DRG) neurons extend their axons toward the dorsolateral part of the spinal cord and enter the spinal cord through the dorsal root entry zone (DREZ). After entering the spinal cord, these axons project into the dorsal mantle layer after a 'waiting period' of a few days. We reve...
journal_title:Cell adhesion & migration
pub_type: 杂志文章,评审
doi:10.4161/cam.3.2.7837
更新日期:2009-04-01 00:00:00
abstract::Podosomes are small, circular adhesions formed by cells such as osteoclasts, macrophages, dendritic cells, and endothelial cells. They comprise a protrusive actin core module and an adhesive ring module composed of integrins and cytoskeletal adaptor proteins such as vinculin and talin. Furthermore, podosomes are assoc...
journal_title:Cell adhesion & migration
pub_type: 杂志文章,评审
doi:10.4161/cam.28182
更新日期:2014-01-01 00:00:00
abstract::Lipocalin-type prostaglandin D synthase (L-PGDS) is one of the most abundant proteins in the cerebrospinal fluid. Nevertheless, its role in the central nervous system is far from clear. Here, we present evidence that L-PGDS induces glial cell migration and morphological changes in vitro and in vivo. We also identified...
journal_title:Cell adhesion & migration
pub_type: 杂志文章
doi:10.4161/cam.20251
更新日期:2012-05-01 00:00:00
abstract::The conserved polarity proteins Par6 and aPKC regulate cell polarization processes. However, increasing evidence also suggests that they play a role in oncogenic progression. During tumor progression, epithelial to mesenchymal transition (EMT) delineates an evolutionary conserved process that converts stationary epith...
journal_title:Cell adhesion & migration
pub_type: 评论,杂志文章
doi:10.4161/cam.25651
更新日期:2013-07-01 00:00:00
abstract::The class-specific transcription factors Knot and Cut act during dendrite arbor development to define the characteristic dendrite branching pattern of the Drosophila class IV dendritic arborisation sensory neurons. Knot mediates dendrite arbor outgrowth and branching via a microtubule-based program that includes upreg...
journal_title:Cell adhesion & migration
pub_type: 杂志文章
doi:10.4161/cam.2.2.6395
更新日期:2008-04-01 00:00:00
abstract::The critical role of migration and invasion in cancer metastasis warrants new therapeutic approaches targeting the machinery regulating cell migration and invasion. While 2-dimensional (2D) models have helped identify a range of adhesion molecules, cytoskeletal components and regulators that are potentially important ...
journal_title:Cell adhesion & migration
pub_type: 杂志文章,评审
doi:10.4161/cam.21559
更新日期:2012-09-01 00:00:00
abstract::The term polarity refers to the differential distribution of the macromolecular elements of a cell, resulting in its asymmetry in function, shape and/or content. Polarity is a fundamental property of all metazoan cells in at least some stages, and is pivotal to processes such as epithelial differentiation (apical/basa...
journal_title:Cell adhesion & migration
pub_type: 杂志文章,评审
doi:10.4161/cam.1.2.4547
更新日期:2007-04-01 00:00:00
abstract::Discoidin domain receptors 1 and 2 (DDR1 and DDR2) are members of the tyrosine kinase receptors activated after binding with collagen. DDRs are implicated in numerous physiological and pathological functions such as proliferation, adhesion and migration. Little is known about the expression of the two receptors in nor...
journal_title:Cell adhesion & migration
pub_type: 杂志文章
doi:10.1080/19336918.2018.1460012
更新日期:2018-01-01 00:00:00
abstract::The physical separation of the embryonic regions that give rise to the tissues and organs of multicellular organisms is a fundamental aspect of morphogenesis. Pioneer experiments by Holtfreter had shown that embryonic cells can sort based on "tissue affinities," which have long been considered to rely on differences i...
journal_title:Cell adhesion & migration
pub_type: 杂志文章,评审
doi:10.4161/19336918.2014.970028
更新日期:2014-01-01 00:00:00
abstract::Cell migration requires a highly coordinated interplay between specialized plasma membrane adhesion complexes and the cytoskeleton. Protein phosphorylation/dephosphorylation modifications regulate many aspects of the integrin-cytoskeleton interdependence, including their coupling, dynamics, and organization to support...
journal_title:Cell adhesion & migration
pub_type: 杂志文章
doi:10.4161/cam.26375
更新日期:2013-09-01 00:00:00
abstract::When trophoblasts migrate and invade in vivo, they do so by interacting with a range of other cell types, extracellular matrix proteins, chemotactic factors and physical forces such as fluid shear stress. These factors combine to influence overall trophoblast migration and invasion into the decidua, which in turn dete...
journal_title:Cell adhesion & migration
pub_type: 杂志文章
doi:10.1080/19336918.2015.1083667
更新日期:2016-03-03 00:00:00
abstract::In this article, I discuss the hallmarks of hypoxia in vitro and in vivo and review work showing that many types of stem cell proliferate more robustly in lowered oxygen. I then discuss recent studies showing that alterations in the levels and the types of cell and substrate adhesion molecules are a notable response t...
journal_title:Cell adhesion & migration
pub_type: 杂志文章,评审
doi:10.4161/cam.19582
更新日期:2012-01-01 00:00:00
abstract::Semaphorin 3A (Sema3A) is a protein identified originally as a diffusible axonal chemorepellent. Sema3A has multifunctional roles in embryonic development, immune regulation, vascularization, and oncogenesis. Bone remodeling consists of two phases: the removal of mineralized bone by osteoclasts and the formation of ne...
journal_title:Cell adhesion & migration
pub_type: 杂志文章,评审
doi:10.4161/cam.27752
更新日期:2014-01-01 00:00:00
abstract:BACKGROUND:Cannabinoids are known to have an anti-tumorous effect, but the underlying mechanisms are only sparsely understood. Mechanical characteristics of tumor cells represent a promising marker to distinguish between tumor cells and the healthy tissue. We tested the hypothesis whether cannabinoids influence the tum...
journal_title:Cell adhesion & migration
pub_type: 杂志文章
doi:10.1080/19336918.2016.1183867
更新日期:2017-01-02 00:00:00