Evidence map›Paper›PMID 41326795›Full record

ArticleNature cell biology2026

RASH3D19 mediates RAS activation through a positive feedback loop in KRAS-mutant cancer.

Warapen Treekitkarnmongkol, Hiroshi Katayama, Deivendran Sankaran, Mei-Chee Tai, Sanchita Rauth, Hanxiao Chen, Tristian Nguyen, Kieko Hara, Fredrik I Thege, Moorthy P Ponnusamy and 10 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

20 authors.

Warapen Treekitkarnmongkol *Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0002-7542-5201
Hiroshi Katayama *Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. HKatayama@mdanderson.org.ORCID http://orcid.org/0000-0003-1821-0260
Deivendran Sankaran *Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0001-5837-2083
Mei-Chee TaiDepartment of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Sanchita RauthDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA.
Hanxiao ChenHubrecht Institute, Royal Netherlands Academy of Arts and Sciences, and Oncode Institute, UMC Utrecht, Utrecht, the Netherlands.
Tristian NguyenDepartment of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0009-0000-4565-1534
Kieko HaraDepartment of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Fredrik I ThegeDepartment of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0002-1822-4526
Moorthy P PonnusamyDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA.
Surinder K BatraDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA.ORCID http://orcid.org/0000-0001-9470-9317
Huamin WangDepartment of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0002-2038-5863
Ignacio I WistubaDepartment of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Thomas D SchmittgenDepartment of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, FL, USA.ORCID http://orcid.org/0000-0002-2812-8546
John V HeymachDepartment of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0001-9068-8942
Scott KopetzDepartment of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0001-9647-3416
Tony HuCenter for Cellular and Molecular Diagnostics, Department of Molecular and Cellular Biology, Tulane University School of Medicine, New Orleans, LA, USA.
Wantong YaoDepartment of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Anirban MaitraDepartment of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0001-7923-9978
Subrata SenDepartment of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. ssen@mdanderson.org.ORCID http://orcid.org/0000-0001-6884-6246

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI DIANE BODURKA · 1985 to 2026
$290.8M
Circulating Biomarkers and Imaging for Early Detection of Pancreatic CancerU01CA214263 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI EUGENE J KOAY, Subrata Sen · 2018 to 2026
$7.2M
Digital Nanoplasmonic Quantification of Tumor-derived Extracellular Vesicles in Plasma MicrosamplesU01CA252965 · NCI · TULANE UNIVERSITY OF LOUISIANA · PI HU, TONY Y., LU, HUA · 2020 to 2024
$3.0M
NCI NIH HHS P30 CA016672NCI NIH HHS U01 CA214263NCI NIH HHS U01 CA252965
6 · The paper itself

Abstract

Therapeutic targeting of mutant KRAS pathways driving cancers is being actively investigated to identify feedback mechanisms responsible for the development of adaptive resistance to mutant KRAS inhibitors undergoing clinical trials. Here we report RASH3D19 as a mediator of RAS pathway activation through a positive feedback loop involving the KRAS-microRNA signalling axis. KRAS-induced miR-222 represses ETS1 expression and downstream transactivation of miR-301a leading to elevation of its target RASH3D19. RASH3D19 facilitates activation of RAS pathways by promoting dimerization and interaction of EGFR with the SOS2, GRB2, SHP2 and GAB1 complex. Genetic deletion of RASH3D19 in mutant KRAS-expressing cancer cells exhibits growth retardation in vitro, in vivo and sensitized pancreatic ductal adenocarcinoma and colorectal cancer cells, organoids and xenografts to mutant KRAS inhibitors, suppressing feedback reactivation of RAS pathways. Therapeutic targeting of RASH3D19 is expected to lead to tumour debulking and alleviating resistance to KRAS inhibitors in mutant KRAS-expressing cancers.

Indexed as

Carcinoma, Pancreatic DuctalColorectal NeoplasmsMutationPancreatic NeoplasmsProto-Oncogene Proteins p21(ras)AnimalsCell Line, TumorCell ProliferationErbB ReceptorsFeedback, PhysiologicalGene Expression Regulation, NeoplasticHumansMiceMice, NudeMicroRNAsSignal TransductionErbB ReceptorsKRAS protein, humanMicroRNAsProto-Oncogene Proteins p21(ras)

Identifiers

PMID41326795
PMCPMC13436838

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.