Evidence map›Paper›PMID 39895630›Full record

ArticleThe Journal of clinical investigation2025

HMGA1 acts as an epigenetic gatekeeper of ASCL2 and Wnt signaling during colon tumorigenesis.

Li Z Luo, Jung-Hyun Kim, Iliana Herrera, Shaoguang Wu, Xinqun Wu, Seong-Sik Park, Juyoung Cho, Leslie Cope, Lingling Xian, Bailey E West and 10 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of clinical investigation, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing 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

8 citing papers in PubMed.

  1. Article
  2. Pan-cancer characterization ofTranslational cancer research · 2026
    Article
  3. Article
  4. Article
  5. Review
  6. Review
  7. Article
  8. 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

20 authors.

Li Z LuoDivision of Hematology, Department of Medicine, the Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Jung-Hyun KimDivision of Hematology, Department of Medicine, the Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Iliana HerreraDivision of Hematology, Department of Medicine, the Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Shaoguang WuDivision of Infectious Diseases, Department of Medicine.
Xinqun WuDivision of Infectious Diseases, Department of Medicine.
Seong-Sik ParkResearch Institute, National Cancer Center, Goyang-si, Gyeonggido, Republic of Korea.
Juyoung ChoResearch Institute, National Cancer Center, Goyang-si, Gyeonggido, Republic of Korea.
Leslie CopeSidney Kimmel Comprehensive Cancer Center, Division of Biostatistics.
Lingling XianDivision of Hematology, Department of Medicine, the Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Bailey E WestDivision of Hematology, Department of Medicine, the Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Julian Calderon-EspinosaDivision of Hematology, Department of Medicine, the Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Joseph KimDivision of Hematology, Department of Medicine, the Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Zanshé ThompsonDivision of Hematology, Department of Medicine, the Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Isha MalooDivision of Hematology, Department of Medicine, the Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Tatianna LarmanDepartment of Pathology and.
Karen L ReddyDepartment of Biological Chemistry, the Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Ying FengDepartment of Oncology, University of Michigan, Ann Arbor, Michigan, USA.
Eric R FearonDepartment of Oncology, University of Michigan, Ann Arbor, Michigan, USA.
Cynthia L SearsDivision of Infectious Diseases, Department of Medicine.
Linda ResarDivision of Hematology, Department of Medicine, the Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

Funding

Clonal Hematopoiesis in Healthy Individuals from Families with Early OnsetCoronary Artery DiseaseR01HL143818 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI BECKER, LEWIS C, RESAR, LINDA M S · 2019 to 2022
$3.3M
Targeting HMGA1 Tumor-Stromal Networks in Pancreatic CarcinogenesisR01CA293602 · NCI · JOHNS HOPKINS UNIVERSITY · PI ELIZABETH M. JAFFEE, Linda M S Resar · 2024 to 2026
$2.1M
High Mobility Group A1 Chromatin Regulators in Colon CarcinogenesisR01CA232741 · NCI · JOHNS HOPKINS UNIVERSITY · PI RESAR, LINDA M S · 2018 to 2022
$1.9M
HMGA Chromatin Remodeling Proteins in Tumor Progression in Myeloproliferative Neoplasms (MPN)R01HL145780 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI MOLITERNO, ALISON R, RESAR, LINDA M S · 2018 to 2021
$1.9M
The HMGA1 Chromatin Regulator in Hematopoietic Stem Cells with AgingR01DK102943 · NIDDK · JOHNS HOPKINS UNIVERSITY · PI RESAR, LINDA M S · 2017 to 2019
$884k
NCI NIH HHS R01 CA232741NCI NIH HHS R01 CA293602NHLBI NIH HHS R01 HL143818NHLBI NIH HHS R01 HL145780NIDDK NIH HHS R01 DK102943
6 · The paper itself

Abstract

Mutated tumor cells undergo changes in chromatin accessibility and gene expression, resulting in aberrant proliferation and differentiation, although how this occurs is unclear. HMGA1 chromatin regulators are abundant in stem cells and oncogenic in diverse tissues; however, their role in colon tumorigenesis is only beginning to emerge. Here, we uncover a previously unknown epigenetic program whereby HMGA1 amplifies Wnt signaling during colon tumorigenesis driven by inflammatory microbiota and/or Adenomatous polyposis coli (Apc) inactivation. Mechanistically, HMGA1 "opens" chromatin to upregulate the stem cell regulator, Ascl2, and downstream Wnt effectors, promoting stem and Paneth-like cell states while depleting differentiated enterocytes. Loss of just one Hmga1 allele within colon epithelium restrains tumorigenesis and Wnt signaling driven by mutant Apc and inflammatory microbiota. However, HMGA1 deficiency has minimal effects in colon epithelium under homeostatic conditions. In human colon cancer cells, HMGA1 directly induces ASCL2 by recruiting activating histone marks. Silencing HMGA1 disrupts oncogenic properties, whereas reexpression of ASCL2 partially rescues these phenotypes. Further, HMGA1 and ASCL2 are coexpressed and upregulated in human colorectal cancer. Together, our results establish HMGA1 as an epigenetic gatekeeper of Wnt signals and cell state under conditions of APC inactivation, illuminating HMGA1 as a potential therapeutic target in colon cancer.

Indexed as

Basic Helix-Loop-Helix ProteinsCarcinogenesisColonic NeoplasmsEpigenesis, GeneticHMGA1a ProteinNeoplasm ProteinsWnt Signaling PathwayAdenomatous Polyposis Coli ProteinAnimalsGene Expression Regulation, NeoplasticHumansMiceMice, KnockoutAdenomatous Polyposis Coli ProteinASCL2 protein, humanAscl2 protein, mouseBasic Helix-Loop-Helix ProteinsHMGA1a ProteinNeoplasm ProteinsColorectal cancerEpigeneticsOncologyTranscription

Identifiers

PMID39895630
PMCPMC11785931

What OpenQuestion holds

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LicenceCC BY
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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.