Evidence map›Paper›PMID 35292783›Full record

ArticleNature cell biology2022

Temporal and spatial topography of cell proliferation in cancer.

Giorgio Gaglia, Sheheryar Kabraji, Danae Rammos, Yang Dai, Ana Verma, Shu Wang, Caitlin E Mills, Mirra Chung, Johann S Bergholz, Shannon Coy and 8 more

Abstract read
In one paragraph

Article in Nature cell biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed
–field-weighted citation impact
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

40 citing papers in PubMed.

  1. Article
  2. The histone deacetylase family in health and disease.Signal transduction and targeted therapy · 2026
    Review
  3. Article
  4. Article
  5. Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Article
  13. Article
  14. Molecular principles underlying aggressive cancers.Signal transduction and targeted therapy · 2025
    Review
  15. Long Non-Coding RNA LINC01123 Facilitates Cholangiocarcinoma Aggravation by Targeting miR-641.The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology · 2025
    Article
  16. Article
  17. Cancer takes many paths through G1/S.Trends in cell biology · 2024
    Review
  18. Article
  19. Article
  20. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

18 authors.

Giorgio Gaglia *Laboratory of Systems Pharmacology, Department of Systems Biology, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-5179-4256
Sheheryar Kabraji *Laboratory of Systems Pharmacology, Department of Systems Biology, Harvard Medical School, Boston, MA, USA. sheheryar_kabraji@dfci.harvard.edu.ORCID http://orcid.org/0000-0002-5315-7103
Danae RammosLaboratory of Systems Pharmacology, Department of Systems Biology, Harvard Medical School, Boston, MA, USA.
Yang DaiLaboratory of Systems Pharmacology, Department of Systems Biology, Harvard Medical School, Boston, MA, USA.
Ana VermaLaboratory of Systems Pharmacology, Department of Systems Biology, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0001-9057-171X
Shu WangLaboratory of Systems Pharmacology, Department of Systems Biology, Harvard Medical School, Boston, MA, USA.
Caitlin E MillsLaboratory of Systems Pharmacology, Department of Systems Biology, Harvard Medical School, Boston, MA, USA.
Mirra ChungLaboratory of Systems Pharmacology, Department of Systems Biology, Harvard Medical School, Boston, MA, USA.
Johann S BergholzDepartment of Cancer Biology, Dana Farber Cancer Institute, Boston, MA, USA.ORCID http://orcid.org/0000-0003-4609-8448
Shannon CoyLaboratory of Systems Pharmacology, Department of Systems Biology, Harvard Medical School, Boston, MA, USA.
Jia-Ren LinLaboratory of Systems Pharmacology, Department of Systems Biology, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0003-4702-7705
Rinath JeselsohnDepartment of Medical Oncology, Dana Farber Cancer Institute, Boston, MA, USA.
Otto MetzgerDepartment of Medical Oncology, Dana Farber Cancer Institute, Boston, MA, USA.
Eric P WinerDepartment of Medical Oncology, Dana Farber Cancer Institute, Boston, MA, USA.
Deborah A DillonDepartment of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Jean J ZhaoDepartment of Cancer Biology, Dana Farber Cancer Institute, Boston, MA, USA.ORCID http://orcid.org/0000-0002-4561-5688
Peter K SorgerLaboratory of Systems Pharmacology, Department of Systems Biology, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-3364-1838
Sandro SantagataLaboratory of Systems Pharmacology, Department of Systems Biology, Harvard Medical School, Boston, MA, USA. ssantagata@bics.bwh.harvard.edu.ORCID http://orcid.org/0000-0002-7528-9668

Funding

VectorP30CA006516 · NCI · DANA-FARBER CANCER INSTITUTE · PI JENNIFER W MACK · 1985 to 2026
$330.6M
Targeting the Vasular SystemP50CA165962 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI WENDY Beth LONDON · 2013 to 2026
$33.5M
Tissue and Pathology CoreP50CA168504 · NCI · DANA-FARBER CANCER INST · PI Nabihah Tayob · 2013 to 2026
$30.1M
Variation in Receptor Tyrosine Kinases and Breast Cancer RiskP50CA089393 · NCI · DANA-FARBER CANCER INSTITUTE · PI WINER, ERIC P · 2000 to 2009
$28.8M
VASCULAR, PULMONARY AND RENAL INJURYT32HL007627 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI GIMBRONE, MICHAEL A, MITCHELL, RICHARD N · 1985 to 2019
$12.7M
TRAINING GRANT IN GENETICST32GM007748 · NIGMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI Anne O'Donnell-Luria, Louise Wilkins-Haug · 1985 to 2026
$12.0M
Integrating targeted therapy and immunotherapy to break through cancerR35CA210057 · NCI · DANA-FARBER CANCER INST · PI Jean Zhao · 2016 to 2026
$10.8M
Systems Pharmacology of Therapeutic and Adverse Responses to ImmuneCheckpoint and Small Molecule DrugsU54CA225088 · NCI · HARVARD MEDICAL SCHOOL · PI SORGER, PETER KARL · 2018 to 2022
$10.8M
Investigating the HSF1 Cancer NetworkR01CA194005 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI SANTAGATA, SANDRO · 2016 to 2020
$2.0M
Elucidating and overcoming endocrine resistance driven by ESR1 mutationsK08CA191058 · NCI · DANA-FARBER CANCER INST · PI JESELSOHN, RINATH M. · 2015 to 2019
$886k
Highly Multiplexed Analysis of Solid Tumors and Liquid Tissues by Cyclic ImmunofluorescenceR41CA224503 · NCI · RARECYTE, INC. · PI KALDJIAN, ERIC · 2018 to 2018
$224k
NCI NIH HHS K08 CA191058NCI NIH HHS P30 CA006516NCI NIH HHS P50 CA089393NCI NIH HHS P50 CA165962NCI NIH HHS P50 CA168504NCI NIH HHS R01 CA194005NCI NIH HHS R35 CA210057NCI NIH HHS R41 CA224503NCI NIH HHS U54 CA225088NHLBI NIH HHS T32 HL007627NIGMS NIH HHS T32 GM007748
6 · The paper itself

Abstract

Proliferation is a fundamental trait of cancer cells, but its properties and spatial organization in tumours are poorly characterized. Here we use highly multiplexed tissue imaging to perform single-cell quantification of cell cycle regulators and then develop robust, multivariate, proliferation metrics. Across diverse cancers, proliferative architecture is organized at two spatial scales: large domains, and smaller niches enriched for specific immune lineages. Some tumour cells express cell cycle regulators in the (canonical) patterns expected of freely growing cells, a phenomenon we refer to as 'cell cycle coherence'. By contrast, the cell cycles of other tumour cell populations are skewed towards specific phases or exhibit non-canonical (incoherent) marker combinations. Coherence varies across space, with changes in oncogene activity and therapeutic intervention, and is associated with aggressive tumour behaviour. Thus, multivariate measures from high-plex tissue images capture clinically significant features of cancer proliferation, a fundamental step in enabling more precise use of anti-cancer therapies.

Indexed as

NeoplasmsCell CycleCell ProliferationHumans

Identifiers

PMID35292783
PMCPMC8959396

What OpenQuestion holds

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Registered trials

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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.