Abstract：
:Cellular senescence suppresses cancer by arresting cells at risk of malignant tumorigenesis. However, senescent cells also secrete molecules that can stimulate premalignant cells to proliferate and form tumors, suggesting the senescence response is antagonistically pleiotropic. We show that premalignant mammary epithelial cells exposed to senescent human fibroblasts in mice irreversibly lose differentiated properties, become invasive and undergo full malignant transformation. Moreover, using cultured mouse or human fibroblasts and non-malignant breast epithelial cells, we show that senescent fibroblasts disrupt epithelial alveolar morphogenesis, functional differentiation and branching morphogenesis. Furthermore, we identify MMP-3 as the major factor responsible for the effects of senescent fibroblasts on branching morphogenesis. Our findings support the idea that senescent cells contribute to age-related pathology, including cancer, and describe a new property of senescent fibroblasts - the ability to alter epithelial differentiation - that might also explain the loss of tissue function and organization that is a hallmark of aging.
journal_name
J Cell Scijournal_title
Journal of cell scienceauthors
Parrinello S,Coppe JP,Krtolica A,Campisi Jdoi
10.1242/jcs.01635keywords:
subject
Has Abstractpub_date
2005-02-01 00:00:00pages
485-96issue
Pt 3eissn
0021-9533issn
1477-9137pii
jcs.01635journal_volume
118pub_type
杂志文章abstract：:Electrical synapses (gap junctions) rapidly transmit signals between neurons and are composed of connexins. In neurons, connexin36 (Cx36) is the most abundant isoform; however, the mechanisms underlying formation of Cx36-containing electrical synapses are unknown. We focus on homocellular and heterocellular gap juncti...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.133066
更新日期：2014-03-15 00:00:00
abstract：:Macroautophagy (autophagy) is a highly conserved intracellular degradation system that is essential for homeostasis in eukaryotic cells. Due to the wide variety of the cytoplasmic targets of autophagy, its dysregulation is associated with many diseases in humans, such as neurodegenerative diseases, heart disease and c...
journal_title：Journal of cell science
pub_type： 杂志文章,评审
doi：10.1242/jcs.196352
更新日期：2017-04-01 00:00:00
abstract：:Phosphoinositides regulate myriad cellular processes, acting as potent signaling molecules in conserved signaling pathways and as organelle gatekeepers that recruit effector proteins to membranes. Phosphoinositide-generating enzymes have been studied extensively in yeast and cultured cells, yet their roles in animal d...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.129031
更新日期：2014-03-01 00:00:00
abstract：:Expression of a dominant negative fragment of the spectrin family member Syne-1 causes an accumulation of binucleate cells, suggesting a role for this protein in cytokinesis. An association of this fragment with the C-terminal tail domain of the kinesin II subunit KIF3B was identified by yeast two-hybrid and co-precip...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.00892
更新日期：2004-02-01 00:00:00
abstract：:Phagocytosis is an actin-based process used by macrophages to clear particles greater than 0.5 microm in diameter. In addition to its role in immunological responses, phagocytosis is also necessary for tissue remodeling and repair. To prevent catastrophic autoimmune reactions, phagocytosis must be tightly regulated. I...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：2002-02-15 00:00:00
abstract：:Stem cell regeneration is crucial for both cell turnover and tissue healing in multicellular organisms. In Arabidopsis roots, a reduced group of cells known as the quiescent center (QC) act as a cell reservoir for surrounding stem cells during both normal growth and in response to external damage. Although cells of th...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.204065
更新日期：2018-01-29 00:00:00
abstract：:It has been claimed repeatedly that gamma-tubulin is exclusively localized at the spindle poles in mitotic animal cells, where it plays a role in microtubule nucleation. In addition to this localization, we have observed a gamma-tubulin-specific staining of the mitotic spindle in several animal cells (human, kangaroo ...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1994-10-01 00:00:00
abstract：:When human cells enter S-phase, overlapping differential inhibitory mechanisms downregulate the replication licensing factors ORC1, CDC6 and Cdt1. Such regulation prevents re-replication so that deregulation of any individual factor alone would not be expected to induce overt re-replication. However, this has been cha...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.041889
更新日期：2009-04-15 00:00:00
abstract：:Ezrin/radixin/moesin (ERM) proteins are thought to play an important role in organizing cortical actin-based cytoskeletons through cross-linkage of actin filaments with integral membrane proteins. Recent in vitro biochemical studies have revealed that ERM proteins phosphorylated on their COOH-terminal threonine residu...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1999-04-01 00:00:00
abstract：:The identification and characterization of scaffold and targeting proteins of the ERK/MAP kinase pathway is important to understand the function and intracellular organization of this pathway. The F-actin binding protein leukocyte-specific protein 1 (LSP1) binds to PKCbetaI and expression of B-LSP1, an LSP1 truncate c...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.00955
更新日期：2004-04-15 00:00:00
abstract：:Cell adhesion molecules of the cadherin family contribute to the regulation of cell shape and fate by mediating strong intercellular adhesion through Ca2+-dependent interaction of their ectodomain and association of their cytoplasmic tail to actin. However, the mechanisms co-ordinating cadherinmediated adhesion with t...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.00857
更新日期：2004-01-15 00:00:00
abstract：:Centriolar satellites are membrane-less structures that localize and move around the centrosome and cilium complex in a microtubule-dependent manner. They play important roles in centrosome- and cilium-related processes, including protein trafficking to the centrosome and cilium complex, and ciliogenesis, and they are...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.196832
更新日期：2017-04-15 00:00:00
abstract：:The ultrastructure of the flagellar apparatus of Chlamydomonas moewusii was examined in detail. Two rhizoplasts were found associated with the basal bodies of this biflagellate and were observed to extend to the central area of the cell. A segment of smooth endoplasmic reticulum ran parallel to each rhizoplast. These ...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1979-10-01 00:00:00
abstract：:C-CAM is a Ca(2+)-independent cell adhesion molecule (CAM) that mediates intercellular adhesion of isolated rat hepatocytes. It is widely distributed in epithelia, where its presence both at lateral cell borders and on apical cell surfaces suggests that it may have diverse biological functions. Two major isoforms, C-C...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1994-05-01 00:00:00
abstract：:The organization of the microfilaments in epidermal cells of Vallisneria leaves was investigated with respect to the induction of cytoplasmic streaming (secondary streaming). In many of the epidermal cells, cytoplasm exhibited rotational streaming along the anticlinal wall of the cell after exposure around the anticli...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1981-04-01 00:00:00
abstract：:The immune synapse (IS) is a specialized structure formed at the contact area between T lymphocytes and antigen-presenting cells (APCs) that is essential for the adaptive immune response. Proper T cell activation requires its polarization towards the APC, which is highly dependent on the tubulin cytoskeleton. Microtub...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.199042
更新日期：2017-04-01 00:00:00
abstract：:Clathrin heavy chain is the structural component of the clathrin triskelion, but unique functions for the two distinct and highly conserved clathrin light chains (CLCa and CLCb, also known as CLTA and CLTB, respectively) have been elusive. Here, we show that following detachment and replating, CLCa is uniquely respons...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.224030
更新日期：2019-05-15 00:00:00
abstract：:We have found that Ehrlich ascites tumour (EAT) cells, deprived of any carbon source, and suspended at a density of 2 X 10(5) cells/cm3, begin to die only after 12 h of starvation, though it is known that under these conditions they lose over 80% of their ATP within 30 min. Moreover, we have found that the viability o...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1985-08-01 00:00:00
abstract：:Gp78 (also known as AMFR and RNF45) is an E3 ubiquitin ligase that targets proteins for proteasomal degradation through endoplasmic reticulum (ER)-associated degradation (ERAD). In this study, we showed that gp78-mediated ubiquitylation is initiated in the peripheral ER. Substrate monoubiquitylation and gp78 CUE domai...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.096396
更新日期：2012-04-01 00:00:00
abstract：:We have previously demonstrated that the subcellular distribution of the adhesion plaque protein, talin, changes dramatically in human platelets in response to platelet activation (Beckerle et al., J. Cell Biol. 109, 3333-3346, 1989). Talin is uniformly distributed throughout the cytoplasm of resting platelets. Howeve...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1993-12-01 00:00:00
abstract：:Phagosomes are formed when phagocytic cells ingest particles such as bacteria, viruses or synthetic beads of different kinds. The environment within the phagosome gradually changes to generate degradative conditions. These changes require multiple interactions between the maturing phagosomes and the endocytic and the ...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1998-01-01 00:00:00
abstract：:Apoptosis, or programmed cell death, involves a cascade of regulatory events leading to the activation of specific proteases. However, the key substrates for these proteases remain to be identified. We previously demonstrated that levels of five unidentified polypeptides were specifically increased in neurons from emb...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1998-03-01 00:00:00
abstract：:The 26S proteasome is the primary protease responsible for degrading misfolded membrane proteins in the endoplasmic reticulum. Here we examine the specific role of beta subunit function on polypeptide cleavage and membrane release of CFTR, a prototypical ER-associated degradation substrate with 12 transmembrane segmen...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.02732
更新日期：2006-01-15 00:00:00
abstract：:Reorganization of the actin cytoskeleton is essential to numerous cellular processes including cell locomotion and cytokinesis. This actin remodeling is regulated in part by Rho family GTPases. Previous studies implicated Trio, a Dbl-homology guanine nucleotide exchange factor with two exchange factor domains, in regu...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：2001-01-01 00:00:00
abstract：:The canonical Wnt/β-catenin signaling pathway regulates cell proliferation in development and adult tissue homeostasis. Dysregulated signaling contributes to human diseases, in particular cancer. Growing evidence suggests a role for clathrin and/or endocytosis in the regulation of this pathway, but conflicting results...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.244467
更新日期：2020-07-09 00:00:00
abstract：:Gp78 (also known as AMFR), an endoplasmic-reticulum (ER)-associated protein degradation (ERAD) E3 ubiquitin ligase, localizes to mitochondria-associated ER and targets the mitofusin (Mfn1 and Mfn2) mitochondrial fusion proteins for degradation. Gp78 is also the cell surface receptor for autocrine motility factor (AMF)...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.171132
更新日期：2015-08-01 00:00:00
abstract：:The cavity systems within chicken erythrocyte nuclei and rat liver nuclei were compared using passive probes of radioactive glycogen and active probes of nuclease-armed-glycogen. The passive probe curves have a form that indicates that they are due to passive occupation of spaces and not due to the effects of a limiti...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1979-06-01 00:00:00
abstract：:The coordinated trafficking and tethering of membrane cargo within cells relies on the function of distinct cytoskeletal motors that are targeted to specific subcellular compartments through interactions with protein adaptors and phospholipids. The unique actin motor myosin VI functions at distinct steps during clathr...
journal_title：Journal of cell science
pub_type： 杂志文章,评审
doi：10.1242/jcs.095554
更新日期：2013-06-15 00:00:00
abstract：:end13-1 was isolated in a screen for endocytosis mutants and has been shown to have a post-internalisation defect in endocytic transport as well as a defect in vacuolar protein sorting (Vps(-) phenotype), leading to secretion of newly synthesised vacuolar proteins. Here we demonstrate that END13 is identical to VPS4, ...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：2001-05-01 00:00:00
abstract：:The main pathology of cystic fibrosis results from obstruction of ducts in several organs by mucous secretions. The cause of this obstruction remains unclear. We have examined expression of the cystic fibrosis transmembrane conductance regulator (CFTR) and of the major pancreatic mucin, MUC1, in primary pancreatic duc...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1993-06-01 00:00:00
