Abstract：
:By operating as both a subunit of the cadherin complex and a key component of Wnt signalling, β-catenin acts as the lynchpin between cell-cell contact and transcriptional regulation of proliferation, coordinating epithelial tissue homeostasis and regeneration. The integration of multiple growth-regulatory inputs with β-catenin signalling has been observed in cancer-derived cells, yet the existence of pathway crosstalk in normal cells is unknown. Using a highly regenerative normal human epithelial culture system that displays contact inhibition, we demonstrate that the receptor tyrosine kinase (RTK)-driven MAPK and Wnt-β-catenin signalling axes form a bidirectional positive-feedback loop to drive cellular proliferation. We show that β-catenin both drives and is regulated by proliferative signalling cues, and its downregulation coincides with the switch from proliferation to contact-inhibited quiescence. We reveal a novel contextual interrelationship whereby positive and negative feedback between three major signalling pathways - EGFR-ERK, PI3K-AKT and Wnt-β-catenin - enable autocrine-regulated tissue homeostasis as an emergent property of physical interactions between cells. Our work has direct implications for normal epithelial tissue homeostasis and provides insight as to how dysregulation of these pathways could drive excessive and sustained cellular growth in disease.
journal_name
J Cell Scijournal_title
Journal of cell scienceauthors
Georgopoulos NT,Kirkwood LA,Southgate Jdoi
10.1242/jcs.150888subject
Has Abstractpub_date
2014-07-01 00:00:00pages
2967-82issue
Pt 13eissn
0021-9533issn
1477-9137pii
jcs.150888journal_volume
127pub_type
杂志文章abstract：:Diploid yeast, like most eukaryotes, can undergo meiotic differentiation to form haploid gametes. Meiotic differentiation and cell growth (proliferation) are mutually exclusive programs, and in yeast the switch between growth and meiosis is controlled by nutritional signals. The signaling pathways that mediate nutriti...
journal_title：Journal of cell science
pub_type： 杂志文章,评审
doi：10.1242/jcs.00460
更新日期：2003-06-01 00:00:00
abstract：:Activation of the yeast cell wall integrity (CWI) pathway induces an adaptive transcriptional programme that is largely dependent on the transcription factor Rlm1 and the mitogen-activated protein kinase (MAPK) Slt2. Upon cell wall stress, the transcription factor Rlm1 is recruited to the promoters of RLM1 and SLT2, a...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.180190
更新日期：2016-04-15 00:00:00
abstract：:In order to replicate, most pathogens need to enter their target cells. Many viruses enter the host cell through an endocytic pathway and hijack endosomes for their journey towards sites of replication. For delivery of their genome to the host cell cytoplasm and to avoid degradation, viruses have to escape this endoso...
journal_title：Journal of cell science
pub_type： 杂志文章,评审
doi：10.1242/jcs.216259
更新日期：2018-08-03 00:00:00
abstract：:Shape changes have been determined in human blood lymphocytes stimulated with OAG, diC8, PMA, colchicine or the hexapeptide fNLPNTL in short-term assays (30 min). Distinct types of shape-change responses were observed. Colchicine was active in generating a relatively small proportion of polarized lymphocytes (front-ta...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1989-07-01 00:00:00
abstract：:The CHO1 antigen is a mitosis-specific kinesin-like motor located at the interzonal region of the spindle. The human cDNA coding for the antigen contains a domain with sequence similarity to the motor domain of kinesin-like protein (Nislow et al., Nature 359, 543, 1992). Here we cloned cDNAs encoding the CHO1 antigen ...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1994-12-01 00:00:00
abstract：:Fluorescence in situ hybridization has demonstrated that chromosomes form individual territories in interphase nuclei. However, this technique is not suitable to determine whether territories are mutually exclusive or interwoven. This notion, however, is essential for understanding functional organizations in the cell...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1999-10-01 00:00:00
abstract：:Mitochondrial homeostasis reflects a dynamic balance between membrane fission and fusion events thought essential for mitochondrial function. We report here that altered expression of the C. elegans BCL2 homolog CED-9 affects both mitochondrial fission and fusion. Although striated muscle cells lacking CED-9 have no a...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.032904
更新日期：2008-10-15 00:00:00
abstract：:Tie2-promoter-mediated loss of peroxisome proliferator-activated receptor gamma (PPARγ, also known as PPARG) in mice leads to osteopetrosis and pulmonary arterial hypertension. Vascular disease is associated with loss of PPARγ in pulmonary microvascular endothelial cells (PMVEC); we evaluated the role of PPARγ in PMVE...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.169011
更新日期：2016-02-15 00:00:00
abstract：:Sustained neurotransmission requires the tight coupling of synaptic vesicle (SV) exocytosis and endocytosis. The mechanisms underlying this coupling are poorly understood. We tested the hypothesis that a cGMP-dependent protein kinase (PKG), encoded by the foraging (for) gene in Drosophila melanogaster, is critical for...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.227165
更新日期：2019-04-05 00:00:00
abstract：:In Saccharomyces cerevisiae, DNA replication stress activates the replication checkpoint, which slows S-phase progression, stabilizes slowed or stalled replication forks, and relieves inhibition of the ribonucleotide reductase (RNR) complex. To identify novel genes that promote cellular viability after replication str...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.03221
更新日期：2006-12-15 00:00:00
abstract：:The signal recognition particle (SRP) is a ribonucleoprotein machine that controls the translation and intracellular sorting of membrane and secreted proteins. The SRP contains a core RNA subunit with which six proteins are assembled. Recent work in both yeast and mammalian cells has identified the nucleolus as a poss...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.01726
更新日期：2005-03-15 00:00:00
abstract：:After birth the proliferation of cardiac cells declines, and further growth of the heart occurs by hypertrophic cell growth. In the present study the cell proliferation capacity of mouse embryonic stem (ES) cells versus neonatal cardiomyocytes and the effects of reactive oxygen species (ROS) on cardiomyogenesis and ca...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.03386
更新日期：2007-03-01 00:00:00
abstract：:Wound healing crucially relies on the mechanical activity of fibroblasts responding to TGFβ1 and to forces transmitted across focal adhesions. Integrin-linked kinase (ILK) is a central adapter recruited to integrin β1 tails in focal adhesions mediating the communication between cells and extracellular matrix. Here, we...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.063024
更新日期：2010-11-15 00:00:00
abstract：:Angiogenesis is critical for vascular remodeling during development and contributes to the pathogenesis of diseases such as cancer. Targeted disruption of several EphB class receptor tyrosine kinases results in vascular remodeling defects during embryogenesis. The role of EphA class receptors in vascular remodeling, h...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.01061
更新日期：2004-04-15 00:00:00
abstract：:Epithelial-to-mesenchymal transition (EMT) of peritoneal mesothelial cells is a pathological process that occurs during peritoneal dialysis. EMT leads to peritoneal fibrosis, ultrafiltration failure and eventually to the discontinuation of therapy. Signaling pathways involved in mesothelial EMT are thus of great inter...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.071647
更新日期：2010-12-15 00:00:00
abstract：:One aspect of human placental function which has not hitherto been studied is the ability of the placenta to digest proteins intracellularly and use the products of hydrolysis to supply its own and foetall complement of hydrolytic enzymes, including the acid proteases cathepsin C and D. We have used trophoblast cells ...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1976-08-01 00:00:00
abstract：:A Sertoli-spermatid coculture model is described in which a large percentage (greater than 76%) of round spermatids remain viable for 48 h and bind to Sertoli cells. The effects of follicle-stimulating hormone (FSH) and testosterone on spermatid binding (expressed as the spermatid density; SD = the number of spermatid...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1991-11-01 00:00:00
abstract：:Phosphoinositides regulate numerous processes in various subcellular compartments. Whereas many stimuli trigger changes in the plasma-membrane PtdIns(4,5)P(2) concentration, little is known about its precursor, PtdIns(4)P, in particular whether there are stimulus-induced alterations independent of those of PtdIns(4,5)...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.060525
更新日期：2010-05-01 00:00:00
abstract：:The function of DAXX, a highly conserved mammalian gene, has remained controversial; this is due, in part, to its identification in a variety of yeast two-hybrid screens. Targeted deletion in the mouse revealed that DAXX is essential for embryonic development. Furthermore, the increased levels of apoptosis observed in...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.00234
更新日期：2003-01-15 00:00:00
abstract：:In mammalian cells, Rho GTPases control the reorganisation of the actin cytoskeleton in response to growth factors. In the cytoplasm, the polymerisation of actin filaments and their organisation into complex architectures is orchestrated by numerous proteins which act either directly, by interacting with actin, or by ...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1996-02-01 00:00:00
abstract：:Spindle pole bodies in the fission yeast Schizosaccharomyces pombe are required during meiosis, not only for spindle formation but also for the assembly of forespore membranes. The spo15 mutant is defective in the formation of forespore membranes, which develop into spore envelopes. The spo15(+)gene encodes a protein ...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：2000-02-01 00:00:00
abstract：:Microdomains have been proposed to explain specificity in the myriad of possible cellular targets of cAMP. Local differences in cAMP levels can be generated by phosphodiesterases, which control the diffusion of cAMP. Here, we address the possibility that adenylyl cyclases, the source of cAMP, can be primary architects...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.058594
更新日期：2010-01-01 00:00:00
abstract：:In Saccharomyces cerevisiae, three classes of sphingolipids contain myo-inositol--inositol phosphorylceramide (IPC), mannosylinositol phosphorylceramide (MIPC) and mannosyldiinositol phosphorylceramide [M(IP)(2)C]. No fission yeast equivalent of Ipt1p, the inositolphosphotransferase that synthesizes M(IP)(2)C from MIP...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.059139
更新日期：2010-05-01 00:00:00
abstract：:It remains unclear how GPI-anchored proteins (GPIAPs), which lack cytoplasmic domains, transduce signals triggered by specific ligation. Such signal transduction has been speculated to require the ligated GPIAP to associate with membrane-spanning proteins that communicate with obligate cytoplasmic proteins. Transient ...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.049346
更新日期：2009-11-01 00:00:00
abstract：:The locomotion of single epidermis cells, grown out from Xenopus laevis tadpole tails has been investigated by time-lapse cinemicrography using phase-contrast and reflection-contrast optics. The cells develop a large, mostly 200-250 nm thick, lamella, which adheres homogeneously to the supporting coverglass and exceed...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1981-12-01 00:00:00
abstract：:The developmental stage at which Dictyostelium discoideum strain v12/M2 cells was inhibited in resuming cell division was monitored by a Coulter counter. Neither vegetative nor pre-aggregating v12/M2 amoebae used as inocula in liquid growth cultures exhibited a delay in recommencing cell division. Inocula prepared fro...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1978-02-01 00:00:00
abstract：:Elementary Ca(2+) signals, such as "Ca(2+) puffs", which arise from the activation of inositol 1,4,5-trisphosphate receptors, are building blocks for local and global Ca(2+) signalling. We characterized Ca(2+) puffs in six cell types that expressed differing ratios of the three inositol 1,4,5-trisphosphate receptor is...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：2001-11-01 00:00:00
abstract：:A correlation between intranuclear distribution of large tumor antigen (T-ag) and proliferative activity in Simian virus 40 (SV40)-transformed cells has been established. Nuclear T-ag was cytochemically detected by the immunoperoxidase reaction. Cell populations with a high growth rate displayed a heterogeneous patter...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1989-07-01 00:00:00
abstract：:Unconventional myosin VIIA (Myo7a) is an actin-based motor molecule that normally functions in the cochlear hair cells of the inner ear. Mutations of MYO7A/Myo7a have been implicated in inherited deafness in both humans and mice. However, there is limited information about the functions of Myo7a outside of the special...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.209924
更新日期：2018-02-22 00:00:00
abstract：:Dyneins are motor proteins that move along microtubules. They have many roles in the cell. They drive the beating of cilia and flagella, move cargos in the cytoplasm and function in the mitotic spindle. Dyneins are large and complex protein machines. Until recently, the way they move was poorly understood. In 2012, tw...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.120725
更新日期：2013-02-01 00:00:00
