Evidence map›Paper›PMID 40189014›Full record

ArticleCancer letters2025

KAP1 promotes gastric adenocarcinoma progression by activating Hippo/YAP1 signaling via binding to HNRNPAB.

Shumei Song, Yibo Fan, Gengyi Zou, Longfei Huo, Janani Kumar, Yuan Li, Ruiping Wang, Enyu Dai, Jiankang Jin, Ailing W Scott and 17 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cancer letters, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. Review
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

27 authors.

Shumei SongDepartment of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Yibo FanDepartment of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Gengyi ZouDepartment of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Longfei HuoDepartment of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Janani KumarEpigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Yuan LiDepartment of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Surgical Oncology and General Surgery, First Hospital of China Medical University, Shenyang, 110001, PR China.
Ruiping WangGenomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Enyu DaiGenomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Jiankang JinDepartment of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Ailing W ScottDepartment of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Shan ShaoDepartment of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Melissa Pool PizziDepartment of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Jody V VykoukalClinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Hiroyuki KatayamaClinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Samir HanashClinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
George A CalinTranslational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Xing ZhangEpigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Min Gyu LeeMolecular & Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Zhenning WangDepartment of Surgical Oncology and General Surgery, First Hospital of China Medical University, Shenyang, 110001, PR China.
Yuan-Hung LoMolecular & Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Qiong GanDepartment of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Rebecca E WatersDepartment of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Feng YinDepartment of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Linghua WangGenomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Xiaodong ChengEpigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Jaffer A AjaniDepartment of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Electronic address: jajani@mdanderson.org.
Shilpa S DharDepartment of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Electronic address: ssdhar@mdanderson.org.

Funding

Common Stem Cell of Origin for Junctional and Gastric AdenocarcinomaR01CA272906 · NCI · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI Jaffer A. Ajani, FRANK D. MCKEON · 2022 to 2026
$4.6M
Molecular dissecting and targeting YAP1 mediated cancer stemness and immune suppression in advanced gastric adenocarcinomaR01CA269685 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI SONG, SHUMEI · 2022 to 2025
$2.2M
Heterozygous KMT2D Loss and MedulloblastomaR01CA262324 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Min Gyu Lee · 2022 to 2026
$2.2M
The Role of Telomere Shortening in MDS-AML Pathogenesis (resubmission)R01CA160433 · NCI · JOHNS HOPKINS UNIVERSITY · PI ARMANIOS, MARY Y · 2012 to 2016
$1.7M
Prediction of Pathologic Complete Response by Gene Expression Profiling in EsophaR01CA138671 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI AJANI, JAFFER A. · 2010 to 2014
$1.5M
Inhibition of Hedgehog Signaling in Gli-1+Adeno CA of the Esoph or GE junctionR01CA172741 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI AJANI, JAFFER A. · 2013 to 2017
$1.4M
Functional characterization of novel oncogenic loci driving progression and immune response in gastrointestinal cancerR00CA263014 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI LO, YUAN-HUNG · 2023 to 2025
$747k
Molecular Biomarkers as Classifiers to Individualize Therapy of Esophagus CancerR21CA129906 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI AJANI, JAFFER A. · 2009 to 2010
$367k
Mechanisms of CDH1-inactivated advanced gastric adenocarcinoma tumorigenesisK99CA286745 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Gengyi Zou · 2025 to 2026
$255k
NCI NIH HHS K99 CA286745NCI NIH HHS R00 CA263014NCI NIH HHS R01 CA138671NCI NIH HHS R01 CA160433NCI NIH HHS R01 CA172741NCI NIH HHS R01 CA262324NCI NIH HHS R01 CA269685NCI NIH HHS R01 CA272906NCI NIH HHS R21 CA129906
6 · The paper itself

Abstract

Gastric adenocarcinoma (GAC) remains a significant global health challenge, with over a million new cases annually. Peritoneal carcinomatosis (PC), detected in ∼20 % of cases at diagnosis and ∼45 % later, is uniformly fatal, with limited treatment options. This study investigated the role of KAP1 in GAC progression, focusing on its interaction with YAP1 and cancer stemness traits. Analysis of over 596 primary GACs and 72 PC samples revealed that high nuclear KAP1 expression correlates with poor prognosis. KAP1 knockdown reduced oncogenic activity and stemness traits in GAC cells. Mechanistically, KAP1 positively regulates YAP1 transcription by binding to its promoter and reducing H3K27ac levels. Mass spectrometry identified an interaction between KAP1 and HNRNPAB, further modulating YAP1 signaling. Expression of the KRAB domain of ZFP568 without its DNA-binding zinc fingers inhibited both KAP1 and YAP1 expression, significantly reducing colony formation and tumor growth in vivo. Additionally, emerging antisense oligonucleotides (ASOs) targeting KAP1 or YAP1 effectively suppressed mouse tumor progression. These findings establish KAP1 as a critical driver of tumor progression in GAC through YAP1 regulation and HNRNPAB interaction, highlighting its potential therapeutic target. This study advances our understanding and offers a preclinical framework to improve outcomes for GAC.

Indexed as

Adaptor Proteins, Signal TransducingAdenocarcinomaProtein Serine-Threonine KinasesStomach NeoplasmsTranscription FactorsTripartite Motif-Containing Protein 28AnimalsCell Line, TumorCell ProliferationDisease ProgressionFemaleGene Expression Regulation, NeoplasticHippo Signaling PathwayHumansMaleMiceAdaptor Proteins, Signal TransducingProtein Serine-Threonine KinasesTranscription FactorsTRIM28 protein, humanTripartite Motif-Containing Protein 28YAP1 protein, humanYAP-Signaling ProteinsAntisense oligonucleotidesCDH1H3K27acPatient derived ascitesSingle cell RNA sequencing

Identifiers

PMID40189014
PMCPMC12165730

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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.