Abstract:
:The molecular mechanisms that couple glycolysis to cancer drug resistance remain unclear. Here we identify an ATP-binding motif within the NADPH oxidase isoform, NOX4, and show that ATP directly binds and negatively regulates NOX4 activity. We find that NOX4 localizes to the inner mitochondria membrane and that subcellular redistribution of ATP levels from the mitochondria act as an allosteric switch to activate NOX4. We provide evidence that NOX4-derived reactive oxygen species (ROS) inhibits P300/CBP-associated factor (PCAF)-dependent acetylation and lysosomal degradation of the pyruvate kinase-M2 isoform (PKM2). Finally, we show that NOX4 silencing, through PKM2, sensitizes cultured and ex vivo freshly isolated human-renal carcinoma cells to drug-induced cell death in xenograft models and ex vivo cultures. These findings highlight yet unidentified insights into the molecular events driving cancer evasive resistance and suggest modulation of ATP levels together with cytotoxic drugs could overcome drug-resistance in glycolytic cancers.
journal_name
Nat Communjournal_title
Nature communicationsauthors
Shanmugasundaram K,Nayak BK,Friedrichs WE,Kaushik D,Rodriguez R,Block Kdoi
10.1038/s41467-017-01106-1subject
Has Abstractpub_date
2017-10-19 00:00:00pages
997issue
1issn
2041-1723pii
10.1038/s41467-017-01106-1journal_volume
8pub_type
杂志文章abstract::Deep subsurface formations (for example, high-temperature oil reservoirs) are candidate sites for carbon capture and storage technology. However, very little is known about how the subsurface microbial community would respond to an increase in CO2 pressure resulting from carbon capture and storage. Here we construct m...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms2998
更新日期:2013-01-01 00:00:00
abstract::Oceanic mesoscale eddies contribute important horizontal heat and salt transports on a global scale. Here we show that eddy transports are mainly due to individual eddy movements. Theoretical and observational analyses indicate that cyclonic and anticyclonic eddies move westwards, and they also move polewards and equa...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms4294
更新日期:2014-01-01 00:00:00
abstract::Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome that elevates the risk of hepatocellular carcinoma (HCC). Although alteration of lipid metabolism has been increasingly recognized as a hallmark of cancer cells, the deregulated metabolic modulation of HCC cells in the NAF...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-019-11274-x
更新日期:2019-07-29 00:00:00
abstract::Untethered small actuators have various applications in multiple fields. However, existing small-scale actuators are very limited in their intractability with their surroundings, respond to only a single type of stimulus and are unable to achieve programmable structural changes under different stimuli. Here, we presen...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-019-12044-5
更新日期:2019-09-09 00:00:00
abstract::While main group elements have four valence orbitals accessible for bonding, quadruple bonding to main group elements is extremely rare. Here we report that main group element boron is able to form quadruple bonding interactions with iron in the BFe(CO)3- anion complex, which has been revealed by quantum chemical inve...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-019-12767-5
更新日期:2019-10-17 00:00:00
abstract::Base editing tools with diversified editing scopes and minimized RNA off-target activities are required for broad applications. Nevertheless, current Streptococcus pyogenes Cas9 (SpCas9)-based adenine base editors (ABEs) with minimized RNA off-target activities display constrained editing scopes with efficient editing...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-020-19730-9
更新日期:2020-11-17 00:00:00
abstract::Understanding the molecular parameters that regulate cross-species transmission and host adaptation of potential pathogens is crucial to control emerging infectious disease. Although microbial pathotype diversity is conventionally associated with gene gain or loss, the role of pathoadaptive nonsynonymous single-nucleo...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms9754
更新日期:2015-10-30 00:00:00
abstract::Novelty-seeking tendencies in adolescents may promote innovation as well as problematic impulsive behaviour, including drug abuse. Previous research has not clarified whether neural hyper- or hypo-responsiveness to anticipated rewards promotes vulnerability in these individuals. Here we use a longitudinal design to tr...
journal_title:Nature communications
pub_type: 杂志文章,多中心研究
doi:10.1038/ncomms14140
更新日期:2017-02-21 00:00:00
abstract::Whole-genome sequencing using sequencing technologies such as Illumina enables the accurate detection of small-scale variants but provides limited information about haplotypes and variants in repetitive regions of the human genome. Single-molecule sequencing (SMS) technologies such as Pacific Biosciences and Oxford Na...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-019-12493-y
更新日期:2019-10-11 00:00:00
abstract::When assembling individual quantum components into a mesoscopic circuit, the interplay between Coulomb interaction and charge granularity breaks down the classical laws of electrical impedance composition. Here we explore experimentally the thermal consequences, and observe an additional quantum mechanism of electroni...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-019-13566-8
更新日期:2019-12-10 00:00:00
abstract::Human-pluripotent-stem-cell-derived kidney cells (hPSC-KCs) have important potential for disease modelling and regeneration. Whether the hPSC-KCs can reconstitute tissue-specific phenotypes is currently unknown. Here we show that hPSC-KCs self-organize into kidney organoids that functionally recapitulate tissue-specif...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms9715
更新日期:2015-10-23 00:00:00
abstract::Optic atrophy 1 (OPA1) is a mitochondrial inner membrane protein that has an important role in mitochondrial fusion and structural integrity. Dysfunctional OPA1 mutations cause atrophy of the optic nerve leading to blindness. Here, we show that OPA1 has an important role in the innate immune system. Using conditional ...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-018-05387-y
更新日期:2018-07-27 00:00:00
abstract::We report the results from the first 5D tomographic diffraction imaging experiment of a complex Ni-Pd/CeO2-ZrO2/Al2O3 catalyst used for methane reforming. This five-dimensional (three spatial, one scattering and one dimension to denote time/imposed state) approach enabled us to track the chemical evolution of many par...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-018-07046-8
更新日期:2018-11-12 00:00:00
abstract::This corrects the article DOI: 10.1038/ncomms14013. ...
journal_title:Nature communications
pub_type: 杂志文章,已发布勘误
doi:10.1038/ncomms15795
更新日期:2017-08-14 00:00:00
abstract::Human ether-a-go-go-related gene (hERG) potassium channels determine cardiac action potential and contraction duration. Human uterine contractions are underpinned by an action potential that also possesses an initial spike followed by prolonged depolarization. Here we show that hERG channel proteins (α-conducting and ...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms5108
更新日期:2014-06-17 00:00:00
abstract::The majority of mammalian genes contain one or more alternative polyadenylation sites. Choice of polyadenylation sites was suggested as one of the underlying mechanisms for generating longer/shorter transcript isoforms. Here, we demonstrate that mature mRNA transcripts can undergo additional cleavage and polyadenylati...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-017-02099-7
更新日期:2017-12-11 00:00:00
abstract::Various quantum applications can be reduced to estimating expectation values, which are inevitably deviated by operational and environmental errors. Although errors can be tackled by quantum error correction, the overheads are far from being affordable for near-term technologies. To alleviate the detrimental effects o...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-020-14376-z
更新日期:2020-01-30 00:00:00
abstract::Many bacteria and most archaea possess a crystalline protein surface layer (S-layer), which surrounds their growing and topologically complicated outer surface. Constructing a macromolecular structure of this scale generally requires localized enzymatic machinery, but a regulatory framework for S-layer assembly has no...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-019-10650-x
更新日期:2019-06-21 00:00:00
abstract::Blends of electron-donating and -accepting organic semiconductors are widely used as photoactive materials in next-generation solar cells and photodetectors. The yield of free charges in these systems is often determined by the separation of interfacial electron-hole pairs, which is expected to depend on the ability o...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms11944
更新日期:2016-06-21 00:00:00
abstract::The molecular mechanisms underlying vascular inflammation and associated inflammatory vascular diseases are not well defined. Here we show that endothelial intracellular adenosine and its key regulator adenosine kinase (ADK) play important roles in vascular inflammation. Pro-inflammatory stimuli lead to endothelial in...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-017-00986-7
更新日期:2017-10-16 00:00:00
abstract::Human social networks are overwhelmingly homophilous: individuals tend to befriend others who are similar to them in terms of a range of physical attributes (e.g., age, gender). Do similarities among friends reflect deeper similarities in how we perceive, interpret, and respond to the world? To test whether friendship...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-017-02722-7
更新日期:2018-01-30 00:00:00
abstract::Despite tremendous importance in catalysis, the design of oxide-metal interface has been hampered by the limited understanding of the nature of interfacial sites and the oxide-metal interaction (OMI). Through construction of well-defined Cu2O/Pt, Cu2O/Ag and Cu2O/Au interfaces, we find that Cu2O nanostructures (NSs) o...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-020-15965-8
更新日期:2020-05-08 00:00:00
abstract::Glacier retreat is a worldwide phenomenon with important consequences for the hydrological cycle and downstream ecosystem structure and functioning. To determine the effects of glacier retreat on aquatic communities, we conducted a 4-year flow manipulation in a tropical glacier-fed stream. Compared with an adjacent re...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms12025
更新日期:2016-06-24 00:00:00
abstract::Recent progress in the understanding of percolation theory points to cation-disordered lithium-excess transition metal oxides as high-capacity lithium-ion cathode materials. Nevertheless, the oxygen redox processes required for these materials to deliver high capacity can trigger oxygen loss, which leads to the format...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-017-01115-0
更新日期:2017-10-17 00:00:00
abstract::Bacterial vaginosis is a condition associated with adverse reproductive outcomes and characterized by a shift from a Lactobacillus-dominant vaginal microbiota to a polymicrobial microbiota, consistently colonized by strains of Gardnerella vaginalis. Metronidazole is the first-line treatment; however, treatment failure...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-020-19880-w
更新日期:2020-12-01 00:00:00
abstract::Intrinsic apoptosis is critical to prevent tumor formation and is engaged by many anti-cancer agents to eliminate tumor cells. BAX and BAK, the two essential mediators of apoptosis, are thought to be regulated through similar mechanisms and act redundantly to drive apoptotic cell death. From an unbiased genome-wide CR...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-018-07309-4
更新日期:2018-11-26 00:00:00
abstract::Isolators, or optical diodes, are devices enabling unidirectional light propagation by using non-reciprocal optical materials, namely materials able to break Lorentz reciprocity. The realization of isolators at terahertz frequencies is a very important open challenge made difficult by the intrinsically lossy propagati...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms11216
更新日期:2016-04-06 00:00:00
abstract::Standard optical tweezers rely on optical forces arising when a focused laser beam interacts with a microscopic particle: scattering forces, pushing the particle along the beam direction, and gradient forces, attracting it towards the high-intensity focal spot. Importantly, the incoming laser beam is not affected by t...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-019-10662-7
更新日期:2019-06-18 00:00:00
abstract::We trained and validated risk prediction models for the three major types of skin cancer- basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and melanoma-on a cross-sectional and longitudinal dataset of 210,000 consented research participants who responded to an online survey covering personal and family histo...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-020-20246-5
更新日期:2021-01-08 00:00:00
abstract::Bacterial contamination of biological channels, catheters or water resources is a major threat to public health, which can be amplified by the ability of bacteria to swim upstream. The mechanisms of this 'rheotaxis', the reorientation with respect to flow gradients, are still poorly understood. Here, we follow individ...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-019-11360-0
更新日期:2019-07-31 00:00:00