Abstract:
: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.
journal_name
Celljournal_title
Cellauthors
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-Sandoi
10.1016/j.cell.2020.11.018subject
Has Abstractpub_date
2021-01-07 00:00:00pages
226-242.e21issue
1eissn
0092-8674issn
1097-4172pii
S0092-8674(20)31535-Xjournal_volume
184pub_type
杂志文章相关文献
CELL文献大全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...
journal_title:Cell
pub_type: 评论,杂志文章
doi:10.1016/j.cell.2015.02.026
更新日期:2015-02-26 00:00:00
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...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/j.cell.2014.07.040
更新日期:2014-09-11 00:00:00
abstract::The Rho family of GTPases control diverse biological processes, including cell morphology and mitogenesis. We have identified WASP, the protein that is defective in Wiskott-Aldrich syndrome (WAS), as a novel effector for CDC42Hs, but not for the other Rho family members, Rac and Rho. This interaction is dependent on t...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/s0092-8674(00)81050-8
更新日期:1996-03-08 00:00:00
abstract::Cell lines stably transfected with metal inducible, MT-fos chimeric genes were used to study the ability of the c-fos gene product, Fos, to act as a transcriptional trans-activator. In 3T3MTfos cells, induction of Fos expression led to specific trans-activation of an AP-1 responsive reporter gene. Induction of Fos exp...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(88)90076-1
更新日期:1988-08-12 00:00:00
abstract::Vertebrate Hoxd genes are sequentially activated during the morphogenesis and pattern formation of the limb. Using the approach of gene disruption via homologous recombination in embryonic stem cells, we have assessed the function of the last gene of the complex, Hoxd-13. Mutant mice displayed skeletal alterations alo...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(93)90378-4
更新日期:1993-11-05 00:00:00
abstract::A family of novel substrates was designed to enable the efficient accumulation of intermediates in site-specific recombination. Strategically placed nicks allow these "suicide substrates" to initiate the reaction but prevent its completion or reversal. Consequently, it has been possible to determine that lambda site-s...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(87)90336-9
更新日期:1987-08-28 00:00:00
abstract::Two cDNAs were isolated whose dimerized products bind specifically to a DNA sequence, kappa E2, located in the immunoglobulin kappa chain enhancer. Both cDNAs share a region of extensive identity to the Drosophila daughterless gene and obvious similarity to a segment in three myc proteins, MyoD, and members of the Dro...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(89)90682-x
更新日期:1989-03-10 00:00:00
abstract::A mechanistic description of metazoan transcription is essential for understanding the molecular processes that govern cellular decisions. To provide structural insights into the DNA recognition step of transcription initiation, we used single-particle electron microscopy (EM) to visualize human TFIID with promoter DN...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/j.cell.2012.12.005
更新日期:2013-01-17 00:00:00
abstract::Multiple proteins act co-operatively in mammalian clathrin-mediated endocytosis (CME) to generate endocytic vesicles from the plasma membrane. The principles controlling the activation and organization of the actin cytoskeleton during mammalian CME are, however, not fully understood. Here, we show that the protein FCH...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/j.cell.2018.05.020
更新日期:2018-07-12 00:00:00
abstract::It has been proposed that the initiator protein RepA is rate limiting for mini-P1 plasmid replication, and that the role of the plasmid copy number control locus is to sequester the initiator and thus reduce replication. This proposal appears inconsistent with the observation that RepA is autoregulated, since the prot...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(88)90468-0
更新日期:1988-02-26 00:00:00
abstract::We mutated, by gene targeting, the endogenous hypoxanthine phosphoribosyl transferase (HPRT) gene in mouse embryo-derived stem (ES) cells. A specialized construct of the neomycin resistance (neor) gene was introduced into an exon of a cloned fragment of the Hprt gene and used to transfect ES cells. Among the G418r col...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(87)90646-5
更新日期:1987-11-06 00:00:00
abstract::Bacteria and archaea have evolved sophisticated adaptive immune systems that reply on CRISPR loci and a diverse cassette of Cas genes that are classified into three main types and at least eleven subtypes. All CRISPR-Cas immune systems operate through three main stages: acquisition, biogenesis, and interference. This ...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/j.cell.2015.09.011
更新日期:2015-09-24 00:00:00
abstract::The in vitro folding pathway of bovine pancreatic trypsin inhibitor (BPTI) has been described previously in terms of the disulfide-bonded intermediates that accumulate during folding of the protein. Folding is slow, occurring in hours at pH 7.3, 25 degrees C. In addition, approximately half of the BPTI molecules becom...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(92)90559-u
更新日期:1992-11-27 00:00:00
abstract::The scrapie (PrPSc) and cellular (PrPC) prion proteins are encoded by the same gene, and their different properties are thought to arise from posttranslational modifications. We have found a phosphatidylinositol glycolipid on both PrPC and PrP 27-30 (derived from PrPSc by limited proteolysis at the amino terminus). Et...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(87)90150-4
更新日期:1987-10-23 00:00:00
abstract::Notch signaling regulates many aspects of metazoan development and tissue renewal. Accordingly, the misregulation or loss of Notch signaling underlies a wide range of human disorders, from developmental syndromes to adult-onset diseases and cancer. Notch signaling is remarkably robust in most tissues even though each ...
journal_title:Cell
pub_type: 杂志文章,评审
doi:10.1016/j.cell.2009.03.045
更新日期:2009-04-17 00:00:00
abstract::We have cloned a Dictyostelium phosphotyrosine phosphatase (PTP1) with a catalytic domain showing approximately 38%-50% amino acid identity to those of other PTPs. PTP1 contains an approximately 99 amino acid insert and bacterially produced PTP1 possesses PTP activity. PTP1 is expressed at a very low level in vegetati...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(92)90597-6
更新日期:1992-11-13 00:00:00
abstract::The elucidation of the genetic code remains among the most influential discoveries in biology. While innumerable studies have validated the general universality of the code and its value in predicting and analyzing protein coding sequences, established and emerging work has also suggested that full genome decryption m...
journal_title:Cell
pub_type: 杂志文章,评审
doi:10.1016/j.cell.2016.09.022
更新日期:2016-12-15 00:00:00
abstract::In the nucleus of eukaryotic cells, RNA decay in the 3'-5' direction is carried out by a complex of exonucleases called the exosome. Surprisingly, the purified exosome shows only weak activity in vitro. Two papers in this issue of Cell, by LaCava et al. (2005) and Wyers et al. (2005), and a third report by Vanacova et...
journal_title:Cell
pub_type: 评论,杂志文章
doi:10.1016/j.cell.2005.05.018
更新日期:2005-06-03 00:00:00
abstract::Negative feedback is a widespread feature of signaling pathways. In an unexpected twist described in this issue, He and colleagues identify a membrane-tethered metalloprotease named Tiki that inhibits Wnt signaling by removing an essential eight-residue fragment from Wnt itself. ...
journal_title:Cell
pub_type: 评论,杂志文章
doi:10.1016/j.cell.2012.06.007
更新日期:2012-06-22 00:00:00
abstract::We have isolated the Drosophila melanogaster homolog (Dint-1) of int-1, a conserved cellular oncogene implicated in viral mammary tumorigenesis in mice. The deduced Dint-1 protein sequence contains 468 amino acids and starts with a hydrophobic leader; it is 54% identical to the int-1 sequence, and all 23 cysteine resi...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(87)90038-9
更新日期:1987-08-14 00:00:00
abstract::We have identified an essential gene, called FIP1, encoding a 327 amino acid protein interacting with yeast poly(A) polymerase (PAP1) in the two-hybrid assay. Recombinant FIP1 protein forms a 1:1 complex with PAP1 in vitro. At 37 degrees C, a thermosensitive allele of FIP1 shows a shortening of poly(A) tails and a dec...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(95)90391-7
更新日期:1995-05-05 00:00:00
abstract::Dentatorubral-pallidoluysian atrophy is a progressive neurodegenerative disease caused by the expansion of a polyglutamine repeats within the Atrophin-1 protein. The in vivo function of Atrophin-1 is unknown. We have characterized a Drosophila gene encoding an Atrophin family protein. Analysis of mutant phenotypes ind...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/s0092-8674(01)00630-4
更新日期:2002-01-11 00:00:00
abstract::Loss-of-function diseases are often caused by a mutation in a protein traversing the secretory pathway that compromises the normal balance between protein folding, trafficking, and degradation. We demonstrate that the innate cellular protein homeostasis, or proteostasis, capacity can be enhanced to fold mutated enzyme...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/j.cell.2008.06.037
更新日期:2008-09-05 00:00:00
abstract::To celebrate a century of X-ray crystallography, I describe how 100 crystal structures influenced chromatin and transcription research. ...
journal_title:Cell
pub_type: 历史文章,杂志文章,评审
doi:10.1016/j.cell.2014.10.047
更新日期:2014-11-20 00:00:00
abstract::Brown and beige adipocytes are specialized cells that express uncoupling protein 1 (UCP1) and dissipate chemical energy as heat. These cells likely possess alternative UCP1-independent thermogenic mechanisms. Here, we identify a secreted enzyme, peptidase M20 domain containing 1 (PM20D1), that is enriched in UCP1(+) v...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/j.cell.2016.05.071
更新日期:2016-07-14 00:00:00
abstract::The bHLH-ZIP protein Mad heterodimerizes with Max as a sequence-specific transcriptional repressor. Mad is rapidly induced upon differentiation, and the associated switch from Myc-Max to Mad-Max heterocomplexes seem to repress genes normally activated by Myc-Max. We have identified two related mammalian cDNAs that enc...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(95)90355-0
更新日期:1995-03-10 00:00:00
abstract::Pseudomonas exotoxin (PE) was used as a probe to study the mechanism by which protein ligands are internalized by mammalian cells. Both biochemical and electron microscopic methods were used to look at the internalization of PE by mouse LM cell fibroblasts. Our data suggest that PE enters cells by receptor-mediated en...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(80)90450-x
更新日期:1980-10-01 00:00:00
abstract::Generation of potent antibodies by a mutation-selection process called affinity maturation is a key component of effective immune responses. Antibodies that protect against highly mutable pathogens must neutralize diverse strains. Developing effective immunization strategies to drive their evolution requires understan...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/j.cell.2015.01.027
更新日期:2015-02-12 00:00:00
abstract::During membrane fusion, the outer leaflets of the two membranes merge first, whereas the distal membrane leaflets remain separate until the opening of a fusion pore. This intermediate stage, called hemifusion, is a critical event shared by exocytosis, protein trafficking, and viral entry. ...
journal_title:Cell
pub_type: 杂志文章,评审
doi:10.1016/j.cell.2005.10.015
更新日期:2005-11-04 00:00:00
abstract::Specific active transcription units on chromosome IV in the salivary glands of Chironomus tentans have been visualized by the Miller spreading technique and in situ by conventional electron microscopy. These units are likely to be located in the two most conspicuous puffs on chromosome IV, Balbiani ring 1 (BR 1) and B...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(79)90324-6
更新日期:1979-08-01 00:00:00