Abstract:
:Although autophagy is being pursued as a therapeutic target in clinical oncology trials, its effects on metastasis, the principal cause of cancer mortality, remain unclear. Here, we utilize mammary cancer models to temporally delete essential autophagy regulators during carcinoma progression. Though genetic ablation of autophagy strongly attenuates primary mammary tumor growth, impaired autophagy promotes spontaneous metastasis and enables the outgrowth of disseminated tumor cells into overt macro-metastases. Transcriptomic analysis reveals that autophagy deficiency elicits a subpopulation of otherwise luminal tumor cells exhibiting basal differentiation traits, which is reversed upon preventing accumulation of the autophagy cargo receptor, Neighbor to BRCA1 (NBR1). Furthermore, pharmacological and genetic induction of autophagy suppresses pro-metastatic differentiation and metastatic outgrowth. Analysis of human breast cancer data reveal that autophagy gene expression inversely correlates with pro-metastatic differentiation signatures and predicts overall and distant metastasis-free survival. Overall, these findings highlight autophagy-dependent control of NBR1 as a key determinant of metastatic progression.
journal_name
Dev Celljournal_title
Developmental cellauthors
Marsh T,Kenific CM,Suresh D,Gonzalez H,Shamir ER,Mei W,Tankka A,Leidal AM,Kalavacherla S,Woo K,Werb Z,Debnath Jdoi
10.1016/j.devcel.2020.01.025subject
Has Abstractpub_date
2020-03-09 00:00:00pages
591-604.e6issue
5eissn
1534-5807issn
1878-1551pii
S1534-5807(20)30057-5journal_volume
52pub_type
杂志文章abstract::T-box genes encode DNA binding transcription factors known to regulate a wide variety of developmental processes during embryogenesis and are present in the genomes of all multicellular animals. Indeed, alongside other more familiar families of developmental regulators such as Hox, Sox, and Pax, T-box genes constitute...
journal_title:Developmental cell
pub_type:
doi:10.1016/s1534-5807(02)00330-1
更新日期:2002-11-01 00:00:00
abstract::Melanocortin 4 receptor (Mc4r) plays a crucial role in the central control of energy homeostasis, but its role in peripheral organs has not been fully explored. We have investigated the roles of hypothalamus-mediated energy metabolism during Xenopus limb regeneration. We report that hypothalamus injury inhibits Xenopu...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2018.07.021
更新日期:2018-08-20 00:00:00
abstract::Preventing inappropriate gene expression in time and space is as fundamental as triggering the activation of tissue- or cell-type-specific factors at the correct developmental stage and in the correct cells. Here, we study the impact of Polycomb repressive complex 2 (PRC2) function on HoxA gene regulation. We analyze ...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2019.05.021
更新日期:2019-07-22 00:00:00
abstract::How cells sense their physical microenvironment remains incompletely understood. In two recent Science articles, Lomakin et al. (2020) and Venturini et al. (2020) demonstrate that progressive nuclear deformation associated with cellular confinement triggers intracellular events that promote cell contractility and migr...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2021.01.002
更新日期:2021-01-25 00:00:00
abstract::The interchromosome domain (ICD) model proposes that genes are selectively positioned at the surfaces of chromosome territories to facilitate their regulation. A paper in the May 13 issue of the Journal of Cell Biology provides evidence that supports a reinterpretation of this model. ...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/s1534-5807(02)00196-x
更新日期:2002-06-01 00:00:00
abstract::Local translation allows spatial control of gene expression. Here, we performed a dual protein-mRNA localization screen, using smFISH on 523 human cell lines expressing GFP-tagged genes. 32 mRNAs displayed specific cytoplasmic localizations with local translation at unexpected locations, including cytoplasmic protrusi...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2020.07.010
更新日期:2020-09-28 00:00:00
abstract::The Hippo (Hpo) signaling pathway controls tissue growth and organ size in species ranging from Drosophila to mammals and is deregulated in a wide range of human cancers. The core pathway consists of the Hpo/Warts (Wts) kinase cassette that phosphorylates and inactivates the transcriptional coactivator Yorkie (Yki). H...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2011.12.011
更新日期:2012-02-14 00:00:00
abstract::The ureteric bud is an epithelial tube that undergoes branching morphogenesis to form the renal collecting system. Although development of a normal kidney depends on proper ureteric bud morphogenesis, the cellular events underlying this process remain obscure. Here, we used time-lapse microscopy together with several ...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2013.09.001
更新日期:2013-11-11 00:00:00
abstract::In the field of breast biology, there is a growing appreciation for the "gatekeeping function" of basal cells during development and disease processes yet mechanisms regulating the generation of these cells are poorly understood. Here, we report that the proliferation of basal cells is controlled by SLIT/ROBO1 signali...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2011.05.012
更新日期:2011-06-14 00:00:00
abstract::Major histocompatibility complex class Ib molecules may play a surprising role in pheromone detection in mammals. ...
journal_title:Developmental cell
pub_type: 评论,杂志文章,评审
doi:10.1016/s1534-5807(03)00066-2
更新日期:2003-03-01 00:00:00
abstract::The ability of the death ligand TRAIL to induce tumor cell apoptosis has led to the development of TRAIL-based cancer therapies. Reporting recently in Molecular Cell, Lu et al. (2014) show that the basis for differential TRAIL responses involves clustering of death receptor complexes by E-cadherin and the actin cytosk...
journal_title:Developmental cell
pub_type: 评论,杂志文章
doi:10.1016/j.devcel.2014.06.031
更新日期:2014-07-14 00:00:00
abstract::The gastrulating vertebrate embryo develops three germlayers: ectoderm, mesoderm, and endoderm. Zebrafish endoderm differentiation starts with the activation of sox17 by casanova (cas). We report that spg (pou2/Oct4) is essential for endoderm formation. Embryos devoid of maternal and zygotic spg function (MZspg) lack ...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/s1534-5807(03)00396-4
更新日期:2004-01-01 00:00:00
abstract::The Drosophila compound eye consists of approximately 750 independently functioning ommatidia, each containing two photoreceptor subpopulations. The outer photoreceptors participate in motion detection, while the inner photoreceptors contribute to color vision. Although the inner photoreceptors, R7 and R8, terminally ...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/s1534-5807(03)00156-4
更新日期:2003-06-01 00:00:00
abstract::Oxysterol binding protein-related proteins (ORPs) are conserved lipid binding polypeptides, enriched at ER contacts sites. ORPs promote non-vesicular lipid transport and work as lipid sensors in the context of many cellular tasks, but the determinants of their distinct localization and function are not understood. Her...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2017.10.031
更新日期:2017-12-04 00:00:00
abstract::All pancreatic endocrine cells, producing glucagon, insulin, somatostatin, or PP, differentiate from Pdx1+ progenitors that transiently express Neurogenin3. To understand whether the competence of pancreatic progenitors changes over time, we generated transgenic mice expressing a tamoxifen-inducible Ngn3 fusion protei...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2007.02.010
更新日期:2007-03-01 00:00:00
abstract::The shape of most complex organ systems arises from the directed migration of cohesive groups of cells. Here, we dissect the role of the chemokine guidance receptor Cxcr4b in regulating the collective migration of one such cohesive tissue, the zebrafish lateral line primordium. Using in vivo imaging, we show that the ...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2006.02.019
更新日期:2006-05-01 00:00:00
abstract::Cell and organelle membranes consist of a complex mixture of phospholipids (PLs) that determine their size, shape, and function. Phosphatidylcholine (PC) is the most abundant phospholipid in eukaryotic membranes, yet how cells sense and regulate its levels in vivo remains unclear. Here we show that PCYT1A, the rate-li...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2018.04.012
更新日期:2018-05-21 00:00:00
abstract::Zebrafish heart regeneration occurs through the activation of cardiomyocyte proliferation in areas of trauma. Here, we show that within 3 hr of ventricular injury, the entire endocardium undergoes morphological changes and induces expression of the retinoic acid (RA)-synthesizing enzyme raldh2. By one day posttrauma, ...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2011.01.010
更新日期:2011-03-15 00:00:00
abstract::Recent data indicate that cystic fibrosis (CF) airway mucus is anaerobic. This suggests that Pseudomonas aeruginosa infection in CF reflects biofilm formation and persistence in an anaerobic environment. P. aeruginosa formed robust anaerobic biofilms, the viability of which requires rhl quorum sensing and nitric oxide...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/s1534-5807(02)00295-2
更新日期:2002-10-01 00:00:00
abstract::Cells that undergo epithelial-to-mesenchymal transitions (EMTs) commonly switch from expressing E-cadherin to N-cadherin. But why this occurs is not well understood. In the current issue of Developmental Cell, Scarpa et al. (2015) identify a reason: cadherin switching controls Rac signaling to determine how cell locom...
journal_title:Developmental cell
pub_type: 评论,杂志文章
doi:10.1016/j.devcel.2015.08.002
更新日期:2015-08-24 00:00:00
abstract::Changes to cell shape and interaction drive animal tissue morphogenesis. Reporting now in Developmental Cell, Del Signore et al. (2018) describe active lengthening of cell-cell contacts by Arp2/3-based actin networks. Through cycles of contact lengthening and shortening, the developing Drosophila eye passes through va...
journal_title:Developmental cell
pub_type: 评论,杂志文章
doi:10.1016/j.devcel.2018.02.003
更新日期:2018-02-26 00:00:00
abstract::In this issue of Developmental Cell, Schuster et al. (2014) describe the signals regulated by the bHLH transcription factor HEC1 during Arabidopsis stem cell maintenance. HEC1 acts antagonistically with other factors, integrating multiple cues to provide a balance between cellular differentiation and proliferation. ...
journal_title:Developmental cell
pub_type: 评论,杂志文章
doi:10.1016/j.devcel.2014.02.006
更新日期:2014-02-24 00:00:00
abstract::Centromere chromatin containing histone H3 variant CENP-A is required for accurate chromosome segregation as a foundation for kinetochore assembly. Human centromere chromatin assembles on a part of the long α-satellite (alphoid) DNA array, where it is flanked by pericentric heterochromatin. Heterochromatin spreads int...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2016.05.006
更新日期:2016-06-06 00:00:00
abstract::A central enigma in epigenetics is how epigenetic factors are guided to specific genomic sites for their function. Previously, we reported that a Piwi-piRNA complex associates with the piRNA-complementary site in the Drosophila genome and regulates its epigenetic state. Here, we report that Piwi-piRNA complexes bind t...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2013.01.023
更新日期:2013-03-11 00:00:00
abstract::Enhancers are the primary determinants of cell identity, but the regulatory components controlling enhancer turnover during lineage commitment remain largely unknown. Here we compare the enhancer landscape, transcriptional factor occupancy, and transcriptomic changes in human fetal and adult hematopoietic stem/progeni...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2015.12.014
更新日期:2016-01-11 00:00:00
abstract::Polarized delivery of signaling and adhesion molecules to the leading edge is required for directional migration of cells. Here, we describe a role for the PIP(2)-synthesizing enzyme, PIPKIγi2, in regulation of exocyst complex control of cell polarity and polarized integrin trafficking during migration. Loss of PIPKIγ...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2011.10.030
更新日期:2012-01-17 00:00:00
abstract::In a recent issue of Molecular Cell, Cairo et al. (2013) report that the spindle checkpoint protein Mad1 shuttles between unattached kinetochores and nuclear pores. Mobile Mad1 inhibits the import receptor Kap121p, thus indirectly changing spindle dynamics. This adds nuclear transport control to the mitotic roles of M...
journal_title:Developmental cell
pub_type: 评论,杂志文章
doi:10.1016/j.devcel.2013.01.003
更新日期:2013-01-28 00:00:00
abstract::Messenger RNAs (mRNAs) are synthesized in the cell nucleus and transported through nuclear pores to the cytoplasm for protein synthesis. Reporting in Nature Cell Biology, Mor et al. now track in living cells in real time the journey of single mRNA molecules as they transit from nucleus to cytoplasm. ...
journal_title:Developmental cell
pub_type: 评论,杂志文章
doi:10.1016/j.devcel.2010.05.021
更新日期:2010-06-15 00:00:00
abstract::Cell stress often triggers inflammation as a protective response to tissue damage or infection. In this issue of Developmental Cell, Sullivan et al. (2020) reveal an unexpected role for TRAIL receptors in ER-stress-induced inflammation. ...
journal_title:Developmental cell
pub_type: 评论,杂志文章
doi:10.1016/j.devcel.2020.03.004
更新日期:2020-03-23 00:00:00
abstract::Cell competition promotes the elimination of weaker cells from a growing population. Here we investigate how cells of Drosophila wing imaginal discs distinguish "winners" from "losers" during cell competition. Using genomic and functional assays, we have identified several factors implicated in the process, including ...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2010.05.010
更新日期:2010-06-15 00:00:00