Evidence map›Paper›PMID 34142064›Full record

ArticleiScience2021

RNA sequencing of long-term label-retaining colon cancer stem cells identifies novel regulators of quiescence.

Joseph L Regan, Dirk Schumacher, Stephanie Staudte, Andreas Steffen, Ralf Lesche, Joern Toedling, Thibaud Jourdan, Johannes Haybaeck, Dominik Mumberg, David Henderson and 5 more

Open access · goldAbstract read
In one paragraph

Article in iScience, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
0.9field-weighted citation impact, top 23% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

12 citing papers in PubMed, 13 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors at 7 institutions in 3 countries.

Joseph L ReganBayer AG, Research & Development, Pharmaceuticals, 13342 Berlin, Germany.
Dirk SchumacherLaboratory of Molecular Tumor Pathology, Charité Universitätsmedizin Berlin, 10117 Berlin, Germany.
Stephanie StaudteBayer AG, Research & Development, Pharmaceuticals, 13342 Berlin, Germany.
Andreas SteffenBayer AG, Research & Development, Pharmaceuticals, 13342 Berlin, Germany.
Ralf LescheBayer AG, Research & Development, Pharmaceuticals, 13342 Berlin, Germany.
Joern ToedlingBayer AG, Research & Development, Pharmaceuticals, 13342 Berlin, Germany.
Thibaud JourdanBayer AG, Research & Development, Pharmaceuticals, 13342 Berlin, Germany.
Johannes HaybaeckInstitute of Pathology, Neuropathology and Molecular Pathology, Medical University of Innsbruck, A-6020 Innsbruck, Austria.
Dominik MumbergBayer AG, Research & Development, Pharmaceuticals, 13342 Berlin, Germany.
David HendersonBayer AG, Research & Development, Pharmaceuticals, 13342 Berlin, Germany.
Balázs GyőrffyDepartment of Bioinformatics, Semmelweis University, 1094 Budapest, Hungary.
Christian R A RegenbrechtLaboratory of Molecular Tumor Pathology, Charité Universitätsmedizin Berlin, 10117 Berlin, Germany.
Ulrich KeilholzCharité Comprehensive Cancer Center, Charité - Universitätsmedizin Berlin, 10117 Berlin, Germany.
Reinhold SchäferCharité Comprehensive Cancer Center, Charité - Universitätsmedizin Berlin, 10117 Berlin, Germany.
Martin LangeBayer AG, Research & Development, Pharmaceuticals, 13342 Berlin, Germany.
Bayer (Germany) · DEGerman Cancer Research Center · DENuvisan (Germany) · DECharité - Universitätsmedizin Berlin · DEInnsbruck Medical University · ATSemmelweis University · HUUniversitätsmedizin Göttingen · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Recent data suggest that therapy-resistant quiescent cancer stem cells (qCSCs) are the source of relapse in colon cancer. Here, using colon cancer patient-derived organoids and xenografts, we identify rare long-term label-retaining qCSCs that can re-enter the cell cycle to generate new tumors. RNA sequencing analyses demonstrated that these cells display the molecular hallmarks of quiescent tissue stem cells, including expression of p53 signaling genes, and are enriched for transcripts common to damage-induced quiescent revival stem cells of the regenerating intestine. In addition, we identify negative regulators of cell cycle, downstream of p53, that we show are indicators of poor prognosis and may be targeted for qCSC abolition in both p53 wild-type and mutant tumors. These data support the temporal inhibition of downstream targets of p53 signaling, in combination with standard-of-care treatments, for the elimination of qCSCs and prevention of relapse in colon cancer.

Indexed as

Cancer stem cellsColon cancerOrganoidsp53 signalingQuiescenceTranscriptomics

Identifiers

PMID34142064
PMCPMC8185225
OpenAlexW3164928061

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.