Evidence map›Paper›PMID 41329526›Full record

ArticleThe Journal of clinical investigation2026

Oncogenic KRAS/ERK/JUNB signaling suppresses differentiation regulator GATA6 in pancreatic cancer.

Zheng Zhong, Xinang Cao, Pei-Ju Liao, Raman Sethi, Jeffrey A Klomp, Clint A Stalnecker, Jinmiao Chen, Yue Wan, Channing J Der, David M Virshup

Abstract read
In one paragraph

Article in The Journal of clinical investigation, 2026. 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. Review
  2. GATA4 loss promotes mutantbioRxiv : the preprint server for biology · 2026
    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

10 authors.

Zheng ZhongProgram in Cancer and Stem Cell Biology, Duke-NUS Medical School, Singapore.
Xinang CaoGenome Institute of Singapore and.
Pei-Ju LiaoProgram in Cancer and Stem Cell Biology, Duke-NUS Medical School, Singapore.
Raman SethiBioinformatics Institute, Agency for Science, Technology and Research (A*STAR), Singapore.
Jeffrey A KlompLineberger Comprehensive Cancer Center and.
Clint A StalneckerLineberger Comprehensive Cancer Center and.
Jinmiao ChenProgram in Cancer and Stem Cell Biology, Duke-NUS Medical School, Singapore.
Yue WanGenome Institute of Singapore and.
Channing J DerLineberger Comprehensive Cancer Center and.
David M VirshupProgram in Cancer and Stem Cell Biology, Duke-NUS Medical School, Singapore.

Funding

SToP Cancer SPORE: Developmental Research ProgramP50CA257911 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Jen Jen Yeh · 2022 to 2026
$12.9M
Washington University SPORE in Pancreatic CancerP50CA196510 · NCI · WASHINGTON UNIVERSITY · PI HAWKINS, WILLIAM G · 2016 to 2020
$10.9M
Project 4: The role of codon bias in RAS tumorigenesisP01CA203657 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI DER, CHANNING J. · 2016 to 2020
$7.9M
Targeting undruggable RAS for cancer treatmentR35CA232113 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI DER, CHANNING J. · 2018 to 2024
$6.3M
BIOLOGICAL ACTIVITY OF RAS ONCOGENESR01CA042978 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI DER, CHANNING J. · 1986 to 2017
$5.9M
Identification of synthetic lethal interactors in pancreatic cancerU01CA199235 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI COX, ADRIENNE D, DER, CHANNING J. · 2015 to 2019
$2.5M
NCI NIH HHS P01 CA203657NCI NIH HHS P50 CA196510NCI NIH HHS P50 CA257911NCI NIH HHS R01 CA042978NCI NIH HHS R35 CA232113NCI NIH HHS U01 CA199235
6 · The paper itself

Abstract

GATA6 is a master regulator of differentiation in the pancreas, and its expression levels determine the 2 main molecular subtypes of pancreatic cancer. High GATA6 levels contribute to the classical pancreatic cancer subtype, which is associated with a higher degree of tumor differentiation and better disease prognosis. However, why GATA6 expression varies across pancreatic cancers and what regulates GATA6 expression remain elusive. Here, we report that oncogenic KRAS-activated ERK signaling suppresses GATA6 transcription in pancreatic cancers. GATA6 mRNA levels inversely correlated with KRAS/ERK activity in pancreatic tumors. A genome-wide CRISPR screen in a GATA6-EGFP reporter knockin cell line identified JUNB as the ERK-regulated transcriptional repressor for GATA6. Active ERK stabilized JUNB protein, while KRAS/ERK inhibition led to ubiquitin-independent proteasomal degradation of JUNB and increased transcription of GATA6. Upregulation of GATA6 enhanced chemosensitivity of pancreatic cancer cells, and KRAS/ERK inhibitors synergized with chemotherapy in a GATA6-dependent manner. Our study identifies how oncogenic KRAS/ERK signaling suppresses GATA6 to cause dedifferentiation in pancreatic cancer. Combining KRAS/ERK inhibitors with standard-of-care chemotherapies could be a promising therapeutic strategy for treating pancreatic cancers.

Indexed as

Extracellular Signal-Regulated MAP KinasesGATA6 Transcription FactorGene Expression Regulation, NeoplasticMAP Kinase Signaling SystemNeoplasm ProteinsPancreatic NeoplasmsProto-Oncogene Proteins p21(ras)Transcription FactorsAnimalsCell DifferentiationCell Line, TumorHumansMiceExtracellular Signal-Regulated MAP KinasesGATA6 protein, humanGATA6 Transcription FactorJunB protein, humanKRAS protein, humanNeoplasm ProteinsProto-Oncogene Proteins p21(ras)Transcription FactorsCancerCell biologyOncologySignal transduction

Identifiers

PMID41329526
PMCPMC12867130

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.