Abstract:
:While autophagy is thought to be an essential process in some cancer cells, it is unknown if or how such cancer cells can circumvent autophagy inhibition. To address this, we developed a CRISPR/Cas9 assay with dynamic live-cell imaging to measure acute effects of knockout (KO) of autophagy genes compared to known essential and non-essential genes. In some cancer cells, autophagy is as essential for cancer cell growth as mRNA transcription or translation or DNA replication. However, even these highly autophagy-dependent cancer cells evolve to circumvent loss of autophagy by upregulating NRF2, which is necessary and sufficient for autophagy-dependent cells to circumvent ATG7 KO and maintain protein homeostasis. Importantly, however, this adaptation increases susceptibly to proteasome inhibitors. These studies identify a common mechanism of acquired resistance to autophagy inhibition and show that selection to avoid tumor cell dependency on autophagy creates new, potentially actionable cancer cell susceptibilities.
journal_name
Dev Celljournal_title
Developmental cellauthors
Towers CG,Fitzwalter BE,Regan D,Goodspeed A,Morgan MJ,Liu CW,Gustafson DL,Thorburn Adoi
10.1016/j.devcel.2019.07.010subject
Has Abstractpub_date
2019-09-23 00:00:00pages
690-703.e6issue
6eissn
1534-5807issn
1878-1551pii
S1534-5807(19)30582-9journal_volume
50pub_type
杂志文章abstract::Pontin and reptin are conserved AAA+ ATPases identified in chromatin-remodeling complexes. In a recent issue of Cell, Venteicher et al. provide new insight into the function of pontin and reptin in telomerase biogenesis, which is important for cellular senescence, aging, and cancer. These unexpected findings have impl...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2008.03.018
更新日期:2008-04-01 00:00:00
abstract::The nervous system is enormously complex, yet the number of cues that control axonal growth is surprisingly meager. Posttranslational modifications amplify diversity, but the degree to which they are employed is unclear. Here, we show that Furin and SKI-1 combine with autocatalytic cleavage and a disulfide bridge to g...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2011.11.022
更新日期:2012-02-14 00:00:00
abstract::The orientation of the mitotic spindle plays a key role in determining whether a polarized cell will divide symmetrically or asymmetrically. In most cell types, cytoplasmic dynein plays a critical role in spindle orientation. However, how dynein directs opposite spindle poles toward distinct and predetermined cell end...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2006.02.018
更新日期:2006-04-01 00:00:00
abstract::Many different intercellular signaling pathways are known but, for most, it is unclear whether they can generate oscillating cell behaviors. Here we use time-lapse analysis of Drosophila embryogenesis to show that oenocytes delaminate from the ectoderm in discrete bursts of three. This pulsatile process has a 1 hour p...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2004.10.016
更新日期:2004-12-01 00:00:00
abstract::Blood vessels form an important interface between the environment and the organism by carrying oxygen and nutrients to all cells and thus determining cellular metabolism. It is therefore not surprising that oxygen and metabolism influence the development of the vascular network. Here, we discuss recent insights regard...
journal_title:Developmental cell
pub_type: 杂志文章,评审
doi:10.1016/j.devcel.2009.01.003
更新日期:2009-02-01 00:00:00
abstract::The generation and shedding of extracellular vesicles (EVs), including exosomes and microvesicles (MVs), by cells has emerged as a form of intercellular communication with important roles in several physiological processes and diseases such as cancer. These membrane-enclosed packets can transfer specific proteins, RNA...
journal_title:Developmental cell
pub_type: 杂志文章,评审
doi:10.1016/j.devcel.2016.04.019
更新日期:2016-05-23 00:00:00
abstract::Selection of the correct targets for myelination and regulation of myelin sheath growth are essential for central nervous system (CNS) formation and function. Through a genetic screen in zebrafish and complementary analyses in mice, we find that loss of oligodendrocyte Neurofascin leads to mistargeting of myelin to ce...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2019.10.016
更新日期:2019-12-16 00:00:00
abstract::Precise cell division control is critical for developmental patterning. For the differentiation of a functional stoma, a cellular valve for efficient gas exchange, the single symmetric division of an immediate precursor is absolutely essential. Yet, the mechanism governing this event remains unclear. Here we report co...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2018.04.010
更新日期:2018-05-07 00:00:00
abstract::The crystal structure of a Wnt morphogen bound to its Frizzled receptor ectodomain provides insights into the evolutionary provenance of this complex fold and offers an explanation for why Wnts utilize both lipid- and protein-mediated contacts to engage Frizzleds. ...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2012.07.011
更新日期:2012-08-14 00:00:00
abstract::Cells in a variety of developmental contexts sense extracellular cues that are given locally on their surfaces, and subsequently amplify the initial signal to achieve cell polarization. Drosophila wing cells acquire planar polarity along the proximal-distal (P-D) axis, in which the amplification of the presumptive cue...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2005.11.016
更新日期:2006-02-01 00:00:00
abstract::Signaling receptors are internalized and regulated by clathrin-mediated endocytosis (CME). Two clathrin light chain isoforms, CLCa and CLCb, are integral components of the endocytic machinery whose differential functions remain unknown. We report that CLCb is specifically upregulated in non-small-cell lung cancer (NSC...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2017.01.007
更新日期:2017-02-06 00:00:00
abstract::To maintain mechanical homeostasis, cells must recognize and respond to changes in cytoskeletal integrity. By imaging live cells expressing fluorescently tagged cytoskeletal proteins, we observed that actin stress fibers undergo local, acute, force-induced elongation and thinning events that compromise their stress tr...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2010.08.008
更新日期:2010-09-14 00:00:00
abstract::The majority of excitatory synaptic transmission in the brain occurs at dendritic spines, which are actin-rich protrusions on the dendrites. The asymmetric nature of these structures suggests that proteins regulating cell polarity might be involved in their formation. Indeed, the polarity protein PAR-3 is required for...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2007.11.020
更新日期:2008-02-01 00:00:00
abstract::Several genes are known to regulate circadian rhythms in Arabidopsis, but the identity of the central oscillator has not been established. LHY and CCA1 are related MYB-like transcription factors proposed to be closely involved. Here we demonstrate that, as shown previously for CCA1, inactivation of LHY shortens the pe...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/s1534-5807(02)00170-3
更新日期:2002-05-01 00:00:00
abstract::TORC1 regulates growth and metabolism, in part, by influencing transcriptional programs. Here, we identify REPTOR and REPTOR-BP as transcription factors downstream of TORC1 that are required for ∼ 90% of the transcriptional induction that occurs upon TORC1 inhibition in Drosophila. Thus, REPTOR and REPTOR-BP are major...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2015.03.013
更新日期:2015-05-04 00:00:00
abstract::The TGF-beta family member Nodal is one of the most potent molecules known to an embryo. Studies on Nodal regulation thus far have focused on its transcription, maturation, and interaction with antagonists. Two recent studies on the role of microRNAs (miRNAs) in Nodal signaling now reveal that something important was ...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2007.09.012
更新日期:2007-10-01 00:00:00
abstract::In response to cellular stress, mitochondria remodel their structure by organelle division and fusion. In this issue of Developmental Cell, Cooper et al. (2014) report that a nuclear protein, cyclin C, is recruited from nuclei to mitochondria upon oxidative stress and promotes mitochondrial division and apoptosis of t...
journal_title:Developmental cell
pub_type: 评论,杂志文章
doi:10.1016/j.devcel.2014.01.010
更新日期:2014-01-27 00:00:00
abstract::The gut absorbs dietary nutrients and provides a barrier to xenobiotics and microbiome metabolites. To cope with toxin exposures, the intestinal epithelium is one of the most rapidly proliferating tissues in the body. The stem cell niche supplies essential signaling factors including Wnt proteins secreted by subepithe...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2018.07.023
更新日期:2018-09-24 00:00:00
abstract::Recent studies have demonstrated that MyoD initiates a feed-forward regulation of skeletal muscle gene expression, predicting that MyoD binds directly to many genes expressed during differentiation. We have used chromatin immunoprecipitation and high-throughput sequencing to identify genome-wide binding of MyoD in sev...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2010.02.014
更新日期:2010-04-20 00:00:00
abstract::The Drosophila lipoprotein particle, Lipophorin, bears lipid-linked morphogens on its surface and is required for long-range signaling activity of Wingless and Hedgehog. Heparan sulfate proteoglycans are also critical for trafficking and signaling of these morphogens. Here we show that Lipophorin interacts with the he...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2007.04.019
更新日期:2007-07-01 00:00:00
abstract::Polarity is a prominent feature of both chemotaxis and cytokinesis. In chemotaxis, polarity is established by local accumulation of PI(3,4,5)P3 at the cell's leading edge, achieved through temporal and spatial regulation of PI3 kinases and the tumor suppressor, PTEN. We find that as migrating D. discoideum cells round...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2005.02.010
更新日期:2005-04-01 00:00:00
abstract::For 20 years, researchers have thought that circadian clocks are defined by feedback loops of transcription and translation. The rediscovery of posttranslational circadian oscillators in diverse organisms forces us to rethink this paradigm. Meanwhile, the original "basic" feedback loops of canonical circadian clocks h...
journal_title:Developmental cell
pub_type: 杂志文章,评审
doi:10.1016/j.devcel.2012.02.007
更新日期:2012-03-13 00:00:00
abstract::Single-gene knockout experiments can fail to reveal function in the context of redundancy, which is frequently observed among duplicated genes (paralogs) with overlapping functions. We discuss the complexity associated with studying paralogs and outline how recent advances in CRISPR will help address the "phenotype ga...
journal_title:Developmental cell
pub_type: 杂志文章,评审
doi:10.1016/j.devcel.2017.09.020
更新日期:2017-10-09 00:00:00
abstract::Lipid droplets are fat storage organelles in cells that physically resemble stable oil-water emulsion droplets. In this issue of Developmental Cell, Ben M'barek et al. (2017) show that the resemblance is more than superficial: physical principles governing emulsion stability also control lipid droplet nucleation and g...
journal_title:Developmental cell
pub_type: 评论,杂志文章,评审
doi:10.1016/j.devcel.2017.06.001
更新日期:2017-06-19 00:00:00
abstract::Regulation of microtubule organizing centers (MTOCs) orchestrates the reorganization of the microtubule (MT) cytoskeleton. In the fission yeast Schizosaccharomyces pombe, an equatorial MTOC (eMTOC) at the cell division site disassembles after cytokinesis, and multiple interphase MTOCs (iMTOCs) appear on the nucleus. H...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/s1534-5807(04)00096-6
更新日期:2004-04-01 00:00:00
abstract::Positioning organs in the body often requires the movement of multiple tissues, yet the molecular and cellular mechanisms coordinating such movements are largely unknown. Here, we show that bidirectional signaling between EphrinB1 and EphB3b coordinates the movements of the hepatic endoderm and adjacent lateral plate ...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2016.10.009
更新日期:2016-11-07 00:00:00
abstract::Brassinosteroids (BRs) are essential hormones for plant growth and development. BRs regulate gene expression by inducing dephosphorylation of two key transcription factors, BZR1 and BZR2/BES1, through a signal transduction pathway that involves cell-surface receptors (BRI1 and BAK1) and a GSK3 kinase (BIN2). How BR-re...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2007.06.009
更新日期:2007-08-01 00:00:00
abstract::To ensure equal chromosome segregation during mitosis, the macromolecular kinetochore must remain attached to depolymerizing microtubules, which drive chromosome movements. How kinetochores associate with depolymerizing microtubules, which undergo dramatic structural changes forming curved protofilaments, has yet to b...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2012.09.012
更新日期:2012-11-13 00:00:00
abstract::Spindle checkpoint silencing is crucial for cell-cycle progression, but mechanisms underlying this process remain mysterious. Two papers, one in this issue of Developmental Cell (Meadows et al., 2011) and one in Current Biology (Rosenberg et al., 2011), begin to show how phosphatase PP1-gamma connects chromosome-micro...
journal_title:Developmental cell
pub_type: 评论,杂志文章
doi:10.1016/j.devcel.2011.05.017
更新日期:2011-06-14 00:00:00
abstract::Phase separation represents an important form of subcellular compartmentalization. However, relatively little is known about how the formation or disassembly of such compartments is regulated. In zebrafish, the Balbiani body (Bb) and the germ plasm (Gp) are intimately linked phase-separated structures essential for ge...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2018.07.009
更新日期:2018-08-06 00:00:00