Evidence map›Paper›PMID 42045570›Full record

ArticleNature cell biology2026

Cancer-associated fibroblasts regulate DNA repair in pancreatic cancer through NDRG1-mediated R-loop processing.

Nina Kozlova, Kayla A Cruz, Antoine A Ruzette, Hanna M Doh, Nicholas A Willis, Su Min Hong, Raul S Gonzalez, Monika Vyas, Laura M Selfors, Stephan Dreyer and 26 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature cell biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Article
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

36 authors.

Nina KozlovaDepartment of Medicine, Cancer Research Institute, Beth Israel Deaconess Medical Center, Boston, MA, USA. kozlovanina@gmail.com.ORCID http://orcid.org/0000-0002-4944-7917
Kayla A Cruz *Department of Medicine, Cancer Research Institute, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Antoine A Ruzette *Department of Systems Biology, Harvard Medical School, Boston, MA, USA.
Hanna M DohDepartment of Medicine, Cancer Research Institute, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Nicholas A WillisDepartment of Medicine, Cancer Research Institute, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Su Min HongDepartment of Medicine, Cancer Research Institute, Beth Israel Deaconess Medical Center, Boston, MA, USA.ORCID http://orcid.org/0009-0006-8472-9924
Raul S GonzalezHarvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0001-5526-4220
Monika VyasHarvard Medical School, Boston, MA, USA.
Laura M SelforsHarvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-1317-7353
Stephan DreyerWest of Scotland Hepatobiliary and Pancreatic Unit and The School of Cancer Sciences, University of Glasgow, Glasgow, UK.
Rosie Upstill-GoddardWest of Scotland Hepatobiliary and Pancreatic Unit and The School of Cancer Sciences, University of Glasgow, Glasgow, UK.
Kerrie L FaiaBlueprint Medicines, Inc., Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-6504-160X
Steve WenglowskyBlueprint Medicines, Inc., Cambridge, MA, USA.
Josh CloseBlueprint Medicines, Inc., Cambridge, MA, USA.ORCID http://orcid.org/0000-0003-0696-3759
Alica BeutelDepartment of Molecular Biology and Biochemistry, University of California Irvine, Irvine, CA, USA.
Zeljka JutricDepartment of Surgery, Division of Hepatobiliary and Pancreas Surgery and Islet Cell Transplantation, University of California Irvine Medical Center, Orange, CA, USA.
Michael U J OliphantHarvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0003-2563-6489
Larysa PolubenDepartment of Medicine, Cancer Research Institute, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Byanjana ThapaDepartment of Medicine, Cancer Research Institute, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Martin S TaylorDepartment of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0003-1560-9276
Venla MustonenFaculty of Biochemistry and Molecular Medicine & Biocenter Oulu, University of Oulu, Oulu, Finland.ORCID http://orcid.org/0000-0002-5124-7711
Pradeep MangalathDepartment of Medicine, Cancer Research Institute, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Christopher J HalbrookDepartment of Molecular Biology and Biochemistry, University of California Irvine, Irvine, CA, USA.ORCID http://orcid.org/0000-0002-3376-3114
Joseph E GrossmanDepartment of Medicine, Cancer Research Institute, Beth Israel Deaconess Medical Center, Boston, MA, USA.ORCID http://orcid.org/0000-0002-2130-2783
Rosa F HwangDepartment of Breast Surgical Oncology, and Department of Surgical Oncology, Division of Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
John G ClohessyDepartment of Medicine, Cancer Research Institute, Beth Israel Deaconess Medical Center, Boston, MA, USA.ORCID http://orcid.org/0000-0001-5186-9775
Salla RuskamoFaculty of Biochemistry and Molecular Medicine & Biocenter Oulu, University of Oulu, Oulu, Finland.
Petri KursulaFaculty of Biochemistry and Molecular Medicine & Biocenter Oulu, University of Oulu, Oulu, Finland.ORCID http://orcid.org/0000-0001-8529-3751
Boryana PetrovaHarvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0001-9996-9353
Naama KanarekHarvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-2068-3908
Philip A ColeHarvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0001-6873-7824
David K ChangWest of Scotland Hepatobiliary and Pancreatic Unit and The School of Cancer Sciences, University of Glasgow, Glasgow, UK.ORCID http://orcid.org/0000-0002-4821-3078
Conor L EvansWellman Center for Photomedicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0003-2185-6505
Simon F NørrelykkeDepartment of Systems Biology, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0001-8302-526X
Ralph ScullyDepartment of Medicine, Cancer Research Institute, Beth Israel Deaconess Medical Center, Boston, MA, USA.ORCID http://orcid.org/0000-0002-5064-0175
Taru MuranenDepartment of Medicine, Cancer Research Institute, Beth Israel Deaconess Medical Center, Boston, MA, USA. tmuranen@bidmc.harvard.edu.ORCID http://orcid.org/0000-0003-4158-9002

Funding

Chemical Approaches to Protein PhosphorylationR01CA074305 · NCI · JOHNS HOPKINS UNIVERSITY · PI COLE, PHILIP A · 2002 to 2025
$8.0M
Stalled replication fork repair in cancer predisposition and cancertherapyR35CA263813 · NCI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI Ralph Scully · 2022 to 2026
$5.1M
ANALYSIS OF BRCA1 RECOMBINATION FUNCTIONSR01CA095175 · NCI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI SCULLY, RALPH · 2002 to 2021
$4.9M
Role of extracellular matrix proteins and tumor stroma in DNA repair and cancer progressionR01CA258372 · NCI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI MURANEN, TARU ELIISA · 2021 to 2025
$2.0M
Regulation of stalled fork repair in mammalian cellsR01GM134425 · NIGMS · BETH ISRAEL DEACONESS MEDICAL CENTER · PI SCULLY, RALPH · 2019 to 2022
$1.4M
Targeting Metabolic Crosstalk in Pancreatic CancerR37CA283575 · NCI · UNIVERSITY OF CALIFORNIA-IRVINE · PI Christopher J. Halbrook · 2024 to 2026
$1.3M
Elucidating structural, mechanistic, and allosteric determinants of mTOR Complex 2 (mTORC2) signaling.K08DK129824 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI TAYLOR, MARTIN S · 2021 to 2025
$853k
American Cancer Society (American Cancer Society, Inc.) RSG-19-0201-CSMBoston Children's Hospital (BCH) BTRECHarvard Medical School BBS graduate programHarvard Medical School Foundry awardHarvard Medical School Foundry AwardNational Pancreas Foundation (NPF) NPF-5615796National Science Foundation (NSF) DGE 2140743NCI NIH HHS R01 CA074305NCI NIH HHS R35 CA263813NIDDK NIH HHS K08 DK129824Pew Charitable Trusts Pew ScholarProstate Cancer Foundation (PCF) 24YOUN29Suomen Kulttuurirahasto (Finnish Cultural Foundation) N/AU.S. Department of Health & Human Services | National Institutes of Health (NIH) 3R35CA242428U.S. Department of Health & Human Services | National Institutes of Health (NIH) R01CA095175U.S. Department of Health & Human Services | National Institutes of Health (NIH) R01CA258372U.S. Department of Health & Human Services | National Institutes of Health (NIH) R01CA74305U.S. Department of Health & Human Services | National Institutes of Health (NIH) R01GM134425U.S. Department of Health & Human Services | National Institutes of Health (NIH) R37CA283575V Foundation for Cancer Research (V Foundation) V2021-026
6 · The paper itself

Abstract

Pancreatic ductal adenocarcinomas (PDACs) are aggressive, stroma-rich tumours. They are unresponsive to treatments, and patients relapse quickly on DNA-damaging chemotherapies. PDAC stroma consists of extracellular matrix proteins (ECM), secreted by cancer-associated fibroblasts (CAFs). Here we show an unexpected link between CAF-secreted ECM proteins and enhanced DNA repair. We identify NDRG1 (N-myc downstream-regulated gene 1) as a key mediator that senses signals from the ECM via adhesion receptors and serum and glucocorticoid-activated kinase. We establish NDRG1 as a DNA repair factor that physically associates with replication forks, maintains DNA replication, resolves stalled forks caused by chemotherapies and is involved in reducing R-loops, RNA-DNA hybrids known to cause genomic instability. NDRG1 is highly expressed in PDAC tumours and its high expression correlates with poor disease-specific survival and poor response to chemotherapy. In conclusion, our data reveal an unexpected role for CAF-secreted ECM proteins in promoting DNA repair via NDRG1, mechanistically linking tumour stroma to replication fork homeostasis and R-loop regulation.

Indexed as

Cancer-Associated FibroblastsCarcinoma, Pancreatic DuctalCell Cycle ProteinsDNA RepairIntracellular Signaling Peptides and ProteinsPancreatic NeoplasmsAnimalsCell Line, TumorDNA ReplicationExtracellular Matrix ProteinsGene Expression Regulation, NeoplasticHumansN-myc Downstream-Regulated Gene 1 ProteinProtein Serine-Threonine KinasesSerum-Glucocorticoid Regulated KinasesSignal TransductionCell Cycle ProteinsExtracellular Matrix ProteinsIntracellular Signaling Peptides and ProteinsN-myc Downstream-Regulated Gene 1 ProteinProtein Serine-Threonine KinasesSerum-Glucocorticoid Regulated Kinases

Identifiers

PMID42045570
PMCPMC13179137

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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.