Evidence map›Paper›PMID 37140208›Full record

ArticleInternational journal of cancer2023

KMT2D links TGF-β signaling to noncanonical activin pathway and regulates pancreatic cancer cell plasticity.

Shuang Lu, Hong Sun Kim, Yubo Cao, Karan Bedi, Lili Zhao, Ishwarya Venkata Narayanan, Brian Magnuson, Yumei Gu, Jing Yang, Zhujun Yi and 14 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in International journal of cancer, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
3.2field-weighted citation impact, top 8% of its field
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

12 citing papers in PubMed, 14 citations in OpenAlex.

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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

24 authors at 5 institutions in 2 countries.

Shuang LuDepartment of Pathology & Clinical Labs, Rogel Cancer Center and Center for RNA Biomedicine, University of Michigan, Ann Arbor, Michigan, USA.
Hong Sun KimDepartment of Pathology & Clinical Labs, Rogel Cancer Center and Center for RNA Biomedicine, University of Michigan, Ann Arbor, Michigan, USA.
Yubo CaoDepartment of Pathology & Clinical Labs, Rogel Cancer Center and Center for RNA Biomedicine, University of Michigan, Ann Arbor, Michigan, USA.
Karan BediDepartment of Radiation Oncology, Rogel Cancer Center and Center for RNA Biomedicine, University of Michigan, Ann Arbor, Michigan, USA.
Lili ZhaoDepartment of Biostatistics, University of Michigan, Ann Arbor, Michigan, USA.
Ishwarya Venkata NarayananDepartment of Radiation Oncology, Rogel Cancer Center and Center for RNA Biomedicine, University of Michigan, Ann Arbor, Michigan, USA.
Brian MagnusonDepartment of Biostatistics, University of Michigan, Ann Arbor, Michigan, USA.
Yumei GuDepartment of Pathology & Clinical Labs, Rogel Cancer Center and Center for RNA Biomedicine, University of Michigan, Ann Arbor, Michigan, USA.
Jing YangDepartment of Pathology & Clinical Labs, Rogel Cancer Center and Center for RNA Biomedicine, University of Michigan, Ann Arbor, Michigan, USA.
Zhujun YiDepartment of Pathology & Clinical Labs, Rogel Cancer Center and Center for RNA Biomedicine, University of Michigan, Ann Arbor, Michigan, USA.
Sepideh BabaniamansourDepartment of Pathology & Clinical Labs, Rogel Cancer Center and Center for RNA Biomedicine, University of Michigan, Ann Arbor, Michigan, USA.
Sargis ShameonDepartment of Pathology & Clinical Labs, Rogel Cancer Center and Center for RNA Biomedicine, University of Michigan, Ann Arbor, Michigan, USA.
Chang XuDepartment of Pathology & Clinical Labs, Rogel Cancer Center and Center for RNA Biomedicine, University of Michigan, Ann Arbor, Michigan, USA.
Michelle T PaulsenDepartment of Radiation Oncology, Rogel Cancer Center and Center for RNA Biomedicine, University of Michigan, Ann Arbor, Michigan, USA.
Ping QiuDepartment of Cardiac Surgery, University of Michigan, Ann Arbor, Michigan, USA.
Sivakumar JeyarajanDepartment of Pathology & Clinical Labs, Rogel Cancer Center and Center for RNA Biomedicine, University of Michigan, Ann Arbor, Michigan, USA.
Mats LjungmanDepartment of Radiation Oncology, Rogel Cancer Center and Center for RNA Biomedicine, University of Michigan, Ann Arbor, Michigan, USA.
Dafydd ThomasDepartment of Pathology & Clinical Labs, Rogel Cancer Center and Center for RNA Biomedicine, University of Michigan, Ann Arbor, Michigan, USA.
Yali DouKeck School of Medicine, University of Southern California, Los Angeles, California, USA.
Howard CrawfordHenry Ford Pancreatic Cancer Center, Detroit, Michigan, USA.
Marina Pasca di MaglianoDepartment of Surgery, University of Michigan, Ann Arbor, Michigan, USA.
Kai GeNational Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Health, Bethesda, Maryland, USA.
Bo YangDepartment of Cardiac Surgery, University of Michigan, Ann Arbor, Michigan, USA.
Jiaqi ShiDepartment of Pathology & Clinical Labs, Rogel Cancer Center and Center for RNA Biomedicine, University of Michigan, Ann Arbor, Michigan, USA.ORCID 0000-0003-4893-1587
University of Michigan · USCentral South University · CNHenry Ford Hospital · USNational Institute of Diabetes and Digestive and Kidney Diseases · USUniversity of Southern California · US

Funding

Regulation of PPARgamma Expression and Adipogenesis by PTIP-Associated FactorsZIADK075003 · NIDDK · NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES · PI GE, KAI · 2009 to 2025
$17.6M
Defining epigenetic signaling to reshape pancreatic tumor microenvironmentR37CA262209 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Jiaqi Shi · 2022 to 2026
$2.3M
Linking epigenetic regulation and TGF-β signaling in pancreatic cancerK08CA234222 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI SHI, JIAQI · 2018 to 2021
$744k
NCI NIH HHS K08 CA234222NCI NIH HHS R37 CA262209
6 · The paper itself

Abstract

Although KMT2D, also known as MLL2, is known to play an essential role in development, differentiation, and tumor suppression, its role in pancreatic cancer development is not well understood. Here, we discovered a novel signaling axis mediated by KMT2D, which links TGF-β to the activin A pathway. We found that TGF-β upregulates a microRNA, miR-147b, which in turn leads to post-transcriptional silencing of KMT2D. Loss of KMT2D induces the expression and secretion of activin A, which activates a noncanonical p38 MAPK-mediated pathway to modulate cancer cell plasticity, promote a mesenchymal phenotype, and enhance tumor invasion and metastasis in mice. We observed a decreased KMT2D expression in human primary and metastatic pancreatic cancer. Furthermore, inhibition or knockdown of activin A reversed the protumoral role of KMT2D loss. These findings support a tumor-suppressive role of KMT2D in pancreatic cancer and identify miR-147b and activin A as novel therapeutic targets.

Indexed as

MicroRNAsPancreatic NeoplasmsActivinsAnimalsCell Line, TumorCell PlasticityHumansMiceTransforming Growth Factor betaActivinsMicroRNAsTransforming Growth Factor betaepithelial-mesenchymal transitionmetastasismiR-147bMLL2tumor suppressor

Identifiers

PMID37140208
PMCPMC10330100
OpenAlexW4368357128

What OpenQuestion holds

Textmetadata
LicenceTDM
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.