Evidence map›Paper›PMID 39366375›Full record

ArticleCancer cell2024

Midkine as a driver of age-related changes and increase in mammary tumorigenesis.

Pengze Yan, Ernesto Rojas Jimenez, Zheqi Li, Triet Bui, Marco Seehawer, Jun Nishida, Pierre Foidart, Laura E Stevens, Yingtian Xie, Miguel Munoz Gomez and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cancer cell, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing 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

34 citing papers in PubMed.

  1. Breast cancer prevention by prophylactic Lalba mRNA-LNP vaccination.Proceedings of the National Academy of Sciences of the United States of America · 2026
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  12. Review
  13. Aging-associated differences in mammary tumor-initiating populations and immune evasion pathways in breast cancer.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  14. Evaluation of targeted and immune combination therapies in a rat model of hormone receptor-positive breast cancer.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  15. Article
  16. Review
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors.

Pengze YanDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
Ernesto Rojas JimenezDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
Zheqi LiDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
Triet BuiDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
Marco SeehawerDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
Jun NishidaDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
Pierre FoidartDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
Laura E StevensDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
Yingtian XieCenter for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Miguel Munoz GomezCenter for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
So Yeon ParkDepartment of Pathology, Seoul National University, Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea.
Henry W LongCenter for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Kornelia PolyakDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA; Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Pathology, Seoul National University, Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea; Harvard Stem Cell Institute, Cambridge, MA 02142, USA. Electronic address: kornelia_polyak@dfci.harvard.edu.

Funding

Targeting intratumor heterogeneity in breast cancerR35CA197623 · NCI · DANA-FARBER CANCER INST · PI KORNELIA POLYAK · 2015 to 2026
$12.4M
Tissue and Pathology CoreP01CA250959 · NCI · DANA-FARBER CANCER INST · PI POLYAK, KORNELIA · 2020 to 2024
$8.6M
Cancer Chemical Biology and Metabolism Training ProgramT32CA236754 · NCI · DANA-FARBER CANCER INST · PI Nika N Danial, THOMAS M ROBERTS · 2019 to 2026
$2.6M
NCI NIH HHS P01 CA250959NCI NIH HHS R35 CA197623NCI NIH HHS T32 CA236754
6 · The paper itself

Abstract

Aging is a pivotal risk factor for cancer, yet the underlying mechanisms remain poorly defined. Here, we explore age-related changes in the rat mammary gland by single-cell multiomics. Our findings include increased epithelial proliferation, loss of luminal identity, and decreased naive B and T cells with age. We discover a luminal progenitor population unique to old rats with profiles reflecting precancerous changes and identify midkine (Mdk) as a gene upregulated with age and a regulator of age-related luminal progenitors. Midkine treatment of young rats mimics age-related changes via activating PI3K-AKT-SREBF1 pathway and promotes nitroso-N-methylurea-induced mammary tumorigenesis. Midkine levels increase with age in human blood and mammary epithelium, and higher MDK in normal breast tissue is associated with higher breast cancer risk in younger women. Our findings reveal a link between aging and susceptibility to tumor initiation and identify midkine as a mediator of age-dependent increase in breast tumorigenesis.

Indexed as

AgingBreast NeoplasmsMidkineAnimalsCarcinogenesisCell ProliferationCell Transformation, NeoplasticFemaleHumansMammary Glands, AnimalMammary Neoplasms, ExperimentalMethylnitrosoureaRatsSignal TransductionMDK protein, humanMethylnitrosoureaMidkineagingbreast cancer riskbreast tumorigenesismammary tumorsmidkinesingle-cell profiling

Identifiers

PMID39366375
PMCPMC11560576

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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.