5-FU promotes stemness of colorectal cancer via p53-mediated WNT/β-catenin pathway activation.

Abstract:

:5-Fluorouracil (5-FU) remains the first-line treatment for colorectal cancer (CRC). Although 5-FU initially de-bulks the tumor mass, recurrence after chemotherapy is the barrier to effective clinical outcomes for CRC patients. Here, we demonstrate that p53 promotes WNT3 transcription, leading to activation of the WNT/β-catenin pathway in ApcMin/+/Lgr5EGFP mice, CRC patient-derived tumor organoids (PDTOs) and patient-derived tumor cells (PDCs). Through this regulation, 5-FU induces activation and enrichment of cancer stem cells (CSCs) in the residual tumors, contributing to recurrence after treatment. Combinatorial treatment of a WNT inhibitor and 5-FU effectively suppresses the CSCs and reduces tumor regrowth after discontinuation of treatment. These findings indicate p53 as a critical mediator of 5-FU-induced CSC activation via the WNT/β-catenin signaling pathway and highlight the significance of combinatorial treatment of WNT inhibitor and 5-FU as a compelling therapeutic strategy to improve the poor outcomes of current 5-FU-based therapies for CRC patients.

journal_name

Nat Commun

journal_title

Nature communications

authors

Cho YH,Ro EJ,Yoon JS,Mizutani T,Kang DW,Park JC,Il Kim T,Clevers H,Choi KY

doi

10.1038/s41467-020-19173-2

subject

Has Abstract

pub_date

2020-10-21 00:00:00

pages

5321

issue

1

issn

2041-1723

pii

10.1038/s41467-020-19173-2

journal_volume

11

pub_type

杂志文章
  • Massive yet grossly underestimated global costs of invasive insects.

    abstract::Insects have presented human society with some of its greatest development challenges by spreading diseases, consuming crops and damaging infrastructure. Despite the massive human and financial toll of invasive insects, cost estimates of their impacts remain sporadic, spatially incomplete and of questionable quality. ...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms12986

    authors: Bradshaw CJ,Leroy B,Bellard C,Roiz D,Albert C,Fournier A,Barbet-Massin M,Salles JM,Simard F,Courchamp F

    更新日期:2016-10-04 00:00:00

  • An artificial primitive mimic of the Gramicidin-A channel.

    abstract::Gramicidin A (gA) is the simplest known natural channel, and important progress in improving conduction activity has previously been obtained with modified natural gAs. However, simple artificial systems mimicking the gA functions are unknown. Here we show that gA can be mimicked using a simple synthetic triazole or '...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms5142

    authors: Barboiu M,Le Duc Y,Gilles A,Cazade PA,Michau M,Marie Legrand Y,van der Lee A,Coasne B,Parvizi P,Post J,Fyles T

    更新日期:2014-06-26 00:00:00

  • Proteolysis of MOB1 by the ubiquitin ligase praja2 attenuates Hippo signalling and supports glioblastoma growth.

    abstract::Human glioblastoma is the most frequent and aggressive form of brain tumour in the adult population. Proteolytic turnover of tumour suppressors by the ubiquitin-proteasome system is a mechanism that tumour cells can adopt to sustain their growth and invasiveness. However, the identity of ubiquitin-proteasome targets a...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms2791

    authors: Lignitto L,Arcella A,Sepe M,Rinaldi L,Delle Donne R,Gallo A,Stefan E,Bachmann VA,Oliva MA,Tiziana Storlazzi C,L'Abbate A,Brunetti A,Gargiulo S,Gramanzini M,Insabato L,Garbi C,Gottesman ME,Feliciello A

    更新日期:2013-01-01 00:00:00

  • SHP-1-mediated inhibitory signals promote responsiveness and anti-tumour functions of natural killer cells.

    abstract::Natural killer (NK) cells are cytotoxic innate lymphoid cells that are involved in immune defense. NK cell reactivity is controlled in part by MHC class I recognition by inhibitory receptors, but the underlying molecular mechanisms remain undefined. Using a mouse model of conditional deletion in NK cells, we show here...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms6108

    authors: Viant C,Fenis A,Chicanne G,Payrastre B,Ugolini S,Vivier E

    更新日期:2014-10-30 00:00:00

  • Superconducting phase diagram of H3S under high magnetic fields.

    abstract::The discovery of superconductivity at 260 K in hydrogen-rich compounds like LaH10 re-invigorated the quest for room temperature superconductivity. Here, we report the temperature dependence of the upper critical fields μ0Hc2(T) of superconducting H3S under a record-high combination of applied pressures up to 160 GPa a...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-019-10552-y

    authors: Mozaffari S,Sun D,Minkov VS,Drozdov AP,Knyazev D,Betts JB,Einaga M,Shimizu K,Eremets MI,Balicas L,Balakirev FF

    更新日期:2019-06-07 00:00:00

  • Nitric oxide enhances Th9 cell differentiation and airway inflammation.

    abstract::Th9 cells protect hosts against helminthic infection but also mediate allergic disease. Here we show that nitric oxide (NO) promotes Th9 cell polarization of murine and human CD4(+) T cells. NO de-represses the tumour suppressor gene p53 via nitrosylation of Mdm2. NO also increases p53-mediated IL-2 production, STAT5 ...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms5575

    authors: Niedbala W,Besnard AG,Nascimento DC,Donate PB,Sonego F,Yip E,Guabiraba R,Chang HD,Fukada SY,Salmond RJ,Schmitt E,Bopp T,Ryffel B,Liew FY

    更新日期:2014-08-07 00:00:00

  • Bending rules for animal propulsion.

    abstract::Animal propulsors such as wings and fins bend during motion and these bending patterns are believed to contribute to the high efficiency of animal movements compared with those of man-made designs. However, efforts to implement flexible designs have been met with contradictory performance results. Consequently, there ...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms4293

    authors: Lucas KN,Johnson N,Beaulieu WT,Cathcart E,Tirrell G,Colin SP,Gemmell BJ,Dabiri JO,Costello JH

    更新日期:2014-01-01 00:00:00

  • Signature of quantum Griffiths singularity state in a layered quasi-one-dimensional superconductor.

    abstract::Quantum Griffiths singularity was theoretically proposed to interpret the phenomenon of divergent dynamical exponent in quantum phase transitions. It has been discovered experimentally in three-dimensional (3D) magnetic metal systems and two-dimensional (2D) superconductors. But, whether this state exists in lower dim...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-018-07123-y

    authors: Zhang E,Zhi J,Zou YC,Ye Z,Ai L,Shi J,Huang C,Liu S,Lin Z,Zheng X,Kang N,Xu H,Wang W,He L,Zou J,Liu J,Mao Z,Xiu F

    更新日期:2018-11-07 00:00:00

  • Common and rare variants associating with serum levels of creatine kinase and lactate dehydrogenase.

    abstract::Creatine kinase (CK) and lactate dehydrogenase (LDH) are widely used markers of tissue damage. To search for sequence variants influencing serum levels of CK and LDH, 28.3 million sequence variants identified through whole-genome sequencing of 2,636 Icelanders were imputed into 63,159 and 98,585 people with CK and LDH...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms10572

    authors: Kristjansson RP,Oddsson A,Helgason H,Sveinbjornsson G,Arnadottir GA,Jensson BO,Jonasdottir A,Jonasdottir A,Bragi Walters G,Sulem G,Oskarsdottir A,Benonisdottir S,Davidsson OB,Masson G,Magnusson OT,Holm H,Sigurdardottir O

    更新日期:2016-02-03 00:00:00

  • Developmental genetic bases behind the independent origin of the tympanic membrane in mammals and diapsids.

    abstract::The amniote middle ear is a classical example of the evolutionary novelty. Although paleontological evidence supports the view that mammals and diapsids (modern reptiles and birds) independently acquired the middle ear after divergence from their common ancestor, the developmental bases of these transformations remain...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms7853

    authors: Kitazawa T,Takechi M,Hirasawa T,Adachi N,Narboux-Nême N,Kume H,Maeda K,Hirai T,Miyagawa-Tomita S,Kurihara Y,Hitomi J,Levi G,Kuratani S,Kurihara H

    更新日期:2015-04-22 00:00:00

  • Atomic scale insights into structure instability and decomposition pathway of methylammonium lead iodide perovskite.

    abstract::Organic-inorganic hybrid perovskites are promising candidates for the next-generation solar cells. Many efforts have been made to study their structures in the search for a better mechanistic understanding to guide the materials optimization. Here, we investigate the structure instability of the single-crystalline CH3...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-018-07177-y

    authors: Chen S,Zhang X,Zhao J,Zhang Y,Kong G,Li Q,Li N,Yu Y,Xu N,Zhang J,Liu K,Zhao Q,Cao J,Feng J,Li X,Qi J,Yu D,Li J,Gao P

    更新日期:2018-11-15 00:00:00

  • Fragmentation in spin ice from magnetic charge injection.

    abstract::The complexity embedded in condensed matter fertilizes the discovery of new states of matter, enriched by ingredients like frustration. Illustrating examples in magnetic systems are Kitaev spin liquids, skyrmions phases, or spin ices. These unconventional ground states support exotic excitations, for example the magne...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-017-00277-1

    authors: Lefrançois E,Cathelin V,Lhotel E,Robert J,Lejay P,Colin CV,Canals B,Damay F,Ollivier J,Fåk B,Chapon LC,Ballou R,Simonet V

    更新日期:2017-08-08 00:00:00

  • A freshwater predator hit twice by the effects of warming across trophic levels.

    abstract::Many ecological responses to climate change have been documented. However, due to indirect effects, some responses can be complex and difficult to predict. For example, our understanding of effects on consumers involving responses on several trophic levels is limited. Here, combining the knowledge of trophic interacti...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms6992

    authors: Jonsson T,Setzer M

    更新日期:2015-01-14 00:00:00

  • Corrupted coordination of epigenetic modifications leads to diverging chromatin states and transcriptional heterogeneity in CLL.

    abstract::Cancer evolution is fueled by epigenetic as well as genetic diversity. In chronic lymphocytic leukemia (CLL), intra-tumoral DNA methylation (DNAme) heterogeneity empowers evolution. Here, to comprehensively study the epigenetic dimension of cancer evolution, we integrate DNAme analysis with histone modification mappin...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-019-09645-5

    authors: Pastore A,Gaiti F,Lu SX,Brand RM,Kulm S,Chaligne R,Gu H,Huang KY,Stamenova EK,Béguelin W,Jiang Y,Schulman RC,Kim KT,Alonso A,Allan JN,Furman RR,Gnirke A,Wu CJ,Melnick AM,Meissner A,Bernstein BE,Abdel-Wahab O,L

    更新日期:2019-04-23 00:00:00

  • Bright monomeric near-infrared fluorescent proteins as tags and biosensors for multiscale imaging.

    abstract::Monomeric near-infrared (NIR) fluorescent proteins (FPs) are in high demand as protein tags and components of biosensors for deep-tissue imaging and multicolour microscopy. We report three bright and spectrally distinct monomeric NIR FPs, termed miRFPs, engineered from bacterial phytochrome, which can be used as easil...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms12405

    authors: Shcherbakova DM,Baloban M,Emelyanov AV,Brenowitz M,Guo P,Verkhusha VV

    更新日期:2016-08-19 00:00:00

  • Intensification of the meridional temperature gradient in the Great Barrier Reef following the Last Glacial Maximum.

    abstract::Tropical south-western Pacific temperatures are of vital importance to the Great Barrier Reef (GBR), but the role of sea surface temperatures (SSTs) in the growth of the GBR since the Last Glacial Maximum remains largely unknown. Here we present records of Sr/Ca and δ(18)O for Last Glacial Maximum and deglacial corals...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms5102

    authors: Felis T,McGregor HV,Linsley BK,Tudhope AW,Gagan MK,Suzuki A,Inoue M,Thomas AL,Esat TM,Thompson WG,Tiwari M,Potts DC,Mudelsee M,Yokoyama Y,Webster JM

    更新日期:2014-06-17 00:00:00

  • Identification of ADAR1 adenosine deaminase dependency in a subset of cancer cells.

    abstract::Systematic exploration of cancer cell vulnerabilities can inform the development of novel cancer therapeutics. Here, through analysis of genome-scale loss-of-function datasets, we identify adenosine deaminase acting on RNA (ADAR or ADAR1) as an essential gene for the survival of a subset of cancer cell lines. ADAR1-de...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-018-07824-4

    authors: Gannon HS,Zou T,Kiessling MK,Gao GF,Cai D,Choi PS,Ivan AP,Buchumenski I,Berger AC,Goldstein JT,Cherniack AD,Vazquez F,Tsherniak A,Levanon EY,Hahn WC,Meyerson M

    更新日期:2018-12-21 00:00:00

  • The ARNT-STAT3 axis regulates the differentiation of intestinal intraepithelial TCRαβ⁺CD8αα⁺ cells.

    abstract::Intestinal intraepithelial T cells contribute to the regulation of inflammatory responses in the intestine; however, the molecular basis for their development and maintenance is unknown. The aryl hydrocarbon receptor complexes with the aryl hydrocarbon receptor nuclear translocator (ARNT) and senses environmental fact...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms3112

    authors: Nakajima K,Maekawa Y,Kataoka K,Ishifune C,Nishida J,Arimochi H,Kitamura A,Yoshimoto T,Tomita S,Nagahiro S,Yasutomo K

    更新日期:2013-01-01 00:00:00

  • Resolution of R-loops by INO80 promotes DNA replication and maintains cancer cell proliferation and viability.

    abstract::Collisions between the DNA replication machinery and co-transcriptional R-loops can impede DNA synthesis and are a major source of genomic instability in cancer cells. How cancer cells deal with R-loops to proliferate is poorly understood. Here we show that the ATP-dependent chromatin remodelling INO80 complex promote...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-020-18306-x

    authors: Prendergast L,McClurg UL,Hristova R,Berlinguer-Palmini R,Greener S,Veitch K,Hernandez I,Pasero P,Rico D,Higgins JMG,Gospodinov A,Papamichos-Chronakis M

    更新日期:2020-09-10 00:00:00

  • RNA degradation by the plant RNA exosome involves both phosphorolytic and hydrolytic activities.

    abstract::The RNA exosome provides eukaryotic cells with an essential 3'-5' exoribonucleolytic activity, which processes or eliminates many classes of RNAs. Its nine-subunit core (Exo9) is structurally related to prokaryotic phosphorolytic exoribonucleases. Yet, yeast and animal Exo9s have lost the primordial phosphorolytic cap...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-017-02066-2

    authors: Sikorska N,Zuber H,Gobert A,Lange H,Gagliardi D

    更新日期:2017-12-18 00:00:00

  • Long-term deep-supercooling of large-volume water and red cell suspensions via surface sealing with immiscible liquids.

    abstract::Supercooling of aqueous solutions is a fundamentally and practically important physical phenomenon with numerous applications in biopreservation and beyond. Under normal conditions, heterogeneous nucleation mechanisms critically prohibit the simultaneous long-term (> 1 week), large volume (> 1 ml), and low temperature...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-018-05636-0

    authors: Huang H,Yarmush ML,Usta OB

    更新日期:2018-08-10 00:00:00

  • miR200-regulated CXCL12β promotes fibroblast heterogeneity and immunosuppression in ovarian cancers.

    abstract::High-grade serous ovarian cancers (HGSOC) have been subdivided into molecular subtypes. The mesenchymal HGSOC subgroup, defined by stromal-related gene signatures, is invariably associated with poor patient survival. We demonstrate that stroma exerts a key function in mesenchymal HGSOC. We highlight stromal heterogene...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-018-03348-z

    authors: Givel AM,Kieffer Y,Scholer-Dahirel A,Sirven P,Cardon M,Pelon F,Magagna I,Gentric G,Costa A,Bonneau C,Mieulet V,Vincent-Salomon A,Mechta-Grigoriou F

    更新日期:2018-03-13 00:00:00

  • Identification of myopia-associated WNT7B polymorphisms provides insights into the mechanism underlying the development of myopia.

    abstract::Myopia can cause severe visual impairment. Here, we report a two-stage genome-wide association study for three myopia-related traits in 9,804 Japanese individuals, which was extended with trans-ethnic replication in 2,674 Chinese and 2,690 Caucasian individuals. We identify WNT7B as a novel susceptibility gene for axi...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms7689

    authors: Miyake M,Yamashiro K,Tabara Y,Suda K,Morooka S,Nakanishi H,Khor CC,Chen P,Qiao F,Nakata I,Akagi-Kurashige Y,Gotoh N,Tsujikawa A,Meguro A,Kusuhara S,Polasek O,Hayward C,Wright AF,Campbell H,Richardson AJ,Schache M

    更新日期:2015-03-31 00:00:00

  • Host STING-dependent MDSC mobilization drives extrinsic radiation resistance.

    abstract::Radiotherapy induces and promotes innate and adaptive immunity in which host STING plays an important role. However, radioresistance in irradiated tumors can also develop, resulting in relapse. Here we report a mechanism by which extrinsic resistance develops after local ablative radiation that relies on the immunosup...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-017-01566-5

    authors: Liang H,Deng L,Hou Y,Meng X,Huang X,Rao E,Zheng W,Mauceri H,Mack M,Xu M,Fu YX,Weichselbaum RR

    更新日期:2017-11-23 00:00:00

  • Genome of The Netherlands population-specific imputations identify an ABCA6 variant associated with cholesterol levels.

    abstract::Variants associated with blood lipid levels may be population-specific. To identify low-frequency variants associated with this phenotype, population-specific reference panels may be used. Here we impute nine large Dutch biobanks (~35,000 samples) with the population-specific reference panel created by the Genome of T...

    journal_title:Nature communications

    pub_type: 杂志文章,meta分析

    doi:10.1038/ncomms7065

    authors: van Leeuwen EM,Karssen LC,Deelen J,Isaacs A,Medina-Gomez C,Mbarek H,Kanterakis A,Trompet S,Postmus I,Verweij N,van Enckevort DJ,Huffman JE,White CC,Feitosa MF,Bartz TM,Manichaikul A,Joshi PK,Peloso GM,Deelen P,van D

    更新日期:2015-03-09 00:00:00

  • An invariability-area relationship sheds new light on the spatial scaling of ecological stability.

    abstract::The spatial scaling of stability is key to understanding ecological sustainability across scales and the sensitivity of ecosystems to habitat destruction. Here we propose the invariability-area relationship (IAR) as a novel approach to investigate the spatial scaling of stability. The shape and slope of IAR are largel...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms15211

    authors: Wang S,Loreau M,Arnoldi JF,Fang J,Rahman KA,Tao S,de Mazancourt C

    更新日期:2017-05-19 00:00:00

  • High-speed AFM height spectroscopy reveals µs-dynamics of unlabeled biomolecules.

    abstract::Dynamics are fundamental to the functions of biomolecules and can occur on a wide range of time and length scales. Here we develop and apply high-speed AFM height spectroscopy (HS-AFM-HS), a technique whereby we monitor the sensing of a HS-AFM tip at a fixed position to directly detect the motions of unlabeled molecul...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-018-07512-3

    authors: Heath GR,Scheuring S

    更新日期:2018-11-26 00:00:00

  • Dynamic beam steering with all-dielectric electro-optic III-V multiple-quantum-well metasurfaces.

    abstract::Tunable metasurfaces enable dynamical control of the key constitutive properties of light at a subwavelength scale. To date, electrically tunable metasurfaces at near-infrared wavelengths have been realized using free carrier modulation, and switching of thermo-optical, liquid crystal and phase change media. However, ...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-019-11598-8

    authors: Wu PC,Pala RA,Kafaie Shirmanesh G,Cheng WH,Sokhoyan R,Grajower M,Alam MZ,Lee D,Atwater HA

    更新日期:2019-08-13 00:00:00

  • Author Correction: Engaging with research impact assessment for an environmental science case study.

    abstract::An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...

    journal_title:Nature communications

    pub_type: 已发布勘误

    doi:10.1038/s41467-019-13141-1

    authors: Fryirs KA,Brierley GJ,Dixon T

    更新日期:2019-11-08 00:00:00

  • Dispersion relation of the collective excitations in a resonantly driven polariton fluid.

    abstract::Exciton-polaritons in semiconductor microcavities constitute the archetypal realization of a quantum fluid of light. Under coherent optical drive, remarkable effects such as superfluidity, dark solitons or the nucleation of vortices have been observed, and can be all understood as specific manifestations of the conden...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-019-11886-3

    authors: Stepanov P,Amelio I,Rousset JG,Bloch J,Lemaître A,Amo A,Minguzzi A,Carusotto I,Richard M

    更新日期:2019-08-27 00:00:00