Evidence map›Paper›PMID 40128178›Full record

ArticleNature communications2025

Targeting the disrupted Hippo signaling to prevent neoplastic renal epithelial cell immune evasion.

Xiangmin Lv, Jiyuan Liu, Jinpeng Ruan, Peichao Chen, Chunbo He, Xingeng Zhao, Cong Huang, Li Chen, Hongbo Wang, Guohua Hua and 13 more

Erratum issuedAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing 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

9 citing papers in PubMed.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

23 authors.

Xiangmin Lv *Vincent Center for Reproductive Biology, Department of Obstetrics and Gynecology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Jiyuan Liu *Vincent Center for Reproductive Biology, Department of Obstetrics and Gynecology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-0372-4106
Jinpeng Ruan *Vincent Center for Reproductive Biology, Department of Obstetrics and Gynecology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Peichao ChenVincent Center for Reproductive Biology, Department of Obstetrics and Gynecology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Chunbo HeVincent Center for Reproductive Biology, Department of Obstetrics and Gynecology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Xingeng ZhaoVincent Center for Reproductive Biology, Department of Obstetrics and Gynecology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Cong HuangVincent Center for Reproductive Biology, Department of Obstetrics and Gynecology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Li ChenVincent Center for Reproductive Biology, Department of Obstetrics and Gynecology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Hongbo WangVincent Center for Reproductive Biology, Department of Obstetrics and Gynecology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Guohua HuaOlson Center for Women's Health, Department of Obstetrics and Gynecology, University of Nebraska Medical Center, Omaha, NE, USA.
Davie ShiVincent Center for Reproductive Biology, Department of Obstetrics and Gynecology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0009-0003-0498-6321
Siyi YangVincent Center for Reproductive Biology, Department of Obstetrics and Gynecology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Madelyn L MonessVincent Center for Reproductive Biology, Department of Obstetrics and Gynecology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Isabelle MontouteVincent Center for Reproductive Biology, Department of Obstetrics and Gynecology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Anjali DharVincent Center for Reproductive Biology, Department of Obstetrics and Gynecology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Xingcheng ChenFred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, USA.
Raj KumarDivision of Hematology and oncology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Lu HuCutaneous Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-1594-8828
Ruslan SadreyevDepartment of Molecular Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Oladapo YekuDivision of Hematology and oncology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-6319-1647
Xu WuCutaneous Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
John S DavisOlson Center for Women's Health, Department of Obstetrics and Gynecology, University of Nebraska Medical Center, Omaha, NE, USA.
Cheng WangVincent Center for Reproductive Biology, Department of Obstetrics and Gynecology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. cwang34@mgh.harvard.edu.ORCID http://orcid.org/0000-0002-0911-8254

Funding

The Hippo/YAP Signaling Pathway in Ovarian High Grade Serous CarcinomaR01CA197976 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI WANG, CHENG · 2016 to 2025
$4.0M
Role of the YAP1-LATS2 negative feedback loop in cervical carcinogenesisR01CA279385 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI Cheng Wang · 2023 to 2026
$1.9M
Novel Mechanisms of Cervical Cancer Development and ProgressionR01CA201500 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI WANG, CHENG · 2016 to 2020
$1.8M
NCI NIH HHS R01 CA197976NCI NIH HHS R01 CA201500NCI NIH HHS R01 CA279385U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) 1R01CA201500U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) 1R0CA1238270U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) 2R01CA197976
6 · The paper itself

Abstract

Large-scale cancer genetic/genomic studies demonstrated that papillary renal cell carcinoma (pRCC) is featured with a frequent shallow deletion of the upstream tumor suppressors of the Hippo/YAP signaling pathway, suggesting that this signaling pathway may play a role in pRCC development. Here we develop a transgenic mouse model with a renal epithelial cell-specific hyperactivation of YAP1 and find that hyperactivation of YAP1 can induce dedifferentiation and transformation of renal tubular epithelial cells leading to the development of pRCC. We analyze at the single-cell resolution the cellular landscape alterations during cancer initiation and progression. Our data indicate that the hyperactivated YAP1, via manipulating multiple signaling pathways, induces epithelial cell transformation, MDSC (Myeloid-derived suppressor cells) accumulation, and pRCC development. Interestingly, we find that depletion of MDSC blocks YAP1-induced kidney overgrowth and tumorigenesis. Inhibiting YAP1 activity with MGH-CP1, a recently developed TEAD inhibitor, impedes MDSC accumulation and suppresses tumor development. Our results identify the disrupted Hippo/YAP signaling as a major contributor to pRCC and suggest that targeting the disrupted Hippo pathway represents a plausible strategy to prevent and treat pRCC.

Indexed as

Adaptor Proteins, Signal TransducingCarcinoma, Renal CellEpithelial CellsKidney NeoplasmsProtein Serine-Threonine KinasesTumor EscapeAnimalsCell Cycle ProteinsCell Transformation, NeoplasticHippo Signaling PathwayHumansMiceMice, TransgenicPhosphoproteinsSignal TransductionTranscription FactorsAdaptor Proteins, Signal TransducingCell Cycle ProteinsPhosphoproteinsProtein Serine-Threonine KinasesTranscription FactorsYap1 protein, mouseYAP-Signaling Proteins

Identifiers

PMID40128178
PMCPMC11933345

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.