Colorectal Cancer Cells Enter a Diapause-like DTP State to Survive Chemotherapy.


:Cancer cells enter a reversible drug-tolerant persister (DTP) state to evade death from chemotherapy and targeted agents. It is increasingly appreciated that DTPs are important drivers of therapy failure and tumor relapse. We combined cellular barcoding and mathematical modeling in patient-derived colorectal cancer models to identify and characterize DTPs in response to chemotherapy. Barcode analysis revealed no loss of clonal complexity of tumors that entered the DTP state and recurred following treatment cessation. Our data fit a mathematical model where all cancer cells, and not a small subpopulation, possess an equipotent capacity to become DTPs. Mechanistically, we determined that DTPs display remarkable transcriptional and functional similarities to diapause, a reversible state of suspended embryonic development triggered by unfavorable environmental conditions. Our study provides insight into how cancer cells use a developmentally conserved mechanism to drive the DTP state, pointing to novel therapeutic opportunities to target DTPs.






Rehman SK,Haynes J,Collignon E,Brown KR,Wang Y,Nixon AML,Bruce JP,Wintersinger JA,Singh Mer A,Lo EBL,Leung C,Lima-Fernandes E,Pedley NM,Soares F,McGibbon S,He HH,Pollet A,Pugh TJ,Haibe-Kains B,Morris Q,Ramalho-San




Has Abstract


2021-01-07 00:00:00
















  • Fertile waters for aging research.

    abstract::The quest to slow aging has come far, and what used to be the domain of science fiction writers and snake oil salesmen may soon become science fact. Innovative new approaches, such as the use of the very short-lived African killifish (Harel et al.), are bridging the translational gap and bring the promise of healthy l...


    pub_type: 评论,杂志文章


    authors: Wang AM,Promislow DEL,Kaeberlein M

    更新日期:2015-02-26 00:00:00

  • P7C3 neuroprotective chemicals function by activating the rate-limiting enzyme in NAD salvage.

    abstract::The P7C3 class of aminopropyl carbazole chemicals fosters the survival of neurons in a variety of rodent models of neurodegeneration or nerve cell injury. To uncover its mechanism of action, an active derivative of P7C3 was modified to contain both a benzophenone for photocrosslinking and an alkyne for CLICK chemistry...


    pub_type: 杂志文章


    authors: Wang G,Han T,Nijhawan D,Theodoropoulos P,Naidoo J,Yadavalli S,Mirzaei H,Pieper AA,Ready JM,McKnight SL

    更新日期:2014-09-11 00:00:00

  • Wiskott-Aldrich syndrome protein, a novel effector for the GTPase CDC42Hs, is implicated in actin polymerization.

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    pub_type: 杂志文章


    authors: Symons M,Derry JM,Karlak B,Jiang S,Lemahieu V,Mccormick F,Francke U,Abo A

    更新日期:1996-03-08 00:00:00

  • The c-Fos protein interacts with c-Jun/AP-1 to stimulate transcription of AP-1 responsive genes.

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    pub_type: 杂志文章


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  • Disruption of the Hoxd-13 gene induces localized heterochrony leading to mice with neotenic limbs.

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    pub_type: 杂志文章


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  • Site-specific recombination intermediates trapped with suicide substrates.

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    pub_type: 杂志文章


    authors: Nunes-Düby SE,Matsumoto L,Landy A

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  • A new DNA binding and dimerization motif in immunoglobulin enhancer binding, daughterless, MyoD, and myc proteins.

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    pub_type: 杂志文章


    authors: Murre C,McCaw PS,Baltimore D

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  • Human TFIID binds to core promoter DNA in a reorganized structural state.

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    pub_type: 杂志文章


    authors: Cianfrocco MA,Kassavetis GA,Grob P,Fang J,Juven-Gershon T,Kadonaga JT,Nogales E

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  • A Flat BAR Protein Promotes Actin Polymerization at the Base of Clathrin-Coated Pits.

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    pub_type: 杂志文章


    authors: Almeida-Souza L,Frank RAW,García-Nafría J,Colussi A,Gunawardana N,Johnson CM,Yu M,Howard G,Andrews B,Vallis Y,McMahon HT

    更新日期:2018-07-12 00:00:00

  • Mini-P1 plasmid replication: the autoregulation-sequestration paradox.

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    pub_type: 杂志文章


    authors: Chattoraj DK,Mason RJ,Wickner SH

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  • Site-directed mutagenesis by gene targeting in mouse embryo-derived stem cells.

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    pub_type: 杂志文章


    authors: Thomas KR,Capecchi MR

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  • SnapShot: CRISPR-RNA-guided adaptive immune systems.

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    pub_type: 杂志文章


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    pub_type: 杂志文章


    authors: Weissman JS,Kim PS

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    pub_type: 杂志文章


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    authors: Kopan R,Ilagan MX

    更新日期:2009-04-17 00:00:00

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    pub_type: 杂志文章,评审


    authors: Brar GA

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    pub_type: 评论,杂志文章


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    pub_type: 评论,杂志文章


    authors: Vincent JP,Magee T

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  • The Drosophila homolog of the mouse mammary oncogene int-1 is identical to the segment polarity gene wingless.

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    authors: Rijsewijk F,Schuermann M,Wagenaar E,Parren P,Weigel D,Nusse R

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  • The FIP1 gene encodes a component of a yeast pre-mRNA polyadenylation factor that directly interacts with poly(A) polymerase.

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    authors: Preker PJ,Lingner J,Minvielle-Sebastia L,Keller W

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    pub_type: 杂志文章


    authors: Zhang S,Xu L,Lee J,Xu T

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    pub_type: 历史文章,杂志文章,评审


    authors: Cramer P

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  • The Secreted Enzyme PM20D1 Regulates Lipidated Amino Acid Uncouplers of Mitochondria.

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    pub_type: 杂志文章


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    pub_type: 杂志文章


    authors: Ayer DE,Lawrence QA,Eisenman RN

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    pub_type: 杂志文章


    authors: FitzGerald D,Morris RE,Saelinger CB

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  • Manipulating the selection forces during affinity maturation to generate cross-reactive HIV antibodies.

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    pub_type: 杂志文章


    authors: Wang S,Mata-Fink J,Kriegsman B,Hanson M,Irvine DJ,Eisen HN,Burton DR,Wittrup KD,Kardar M,Chakraborty AK

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    pub_type: 杂志文章,评审


    authors: Chernomordik LV,Kozlov MM

    更新日期:2005-11-04 00:00:00

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    pub_type: 杂志文章


    authors: Lamb MM,Daneholt B

    更新日期:1979-08-01 00:00:00