Evidence map›Paper›PMID 40742309›Full record

ArticleCancer research2025

Oxytocin Receptor Regulates the Hippo/YAP Axis to Drive Hepatocarcinogenesis.

Huijie Yang, Jiayao Cui, Peng Su, Xiujie Cui, Haojie Guo, Penghe Yang, Shuqing Zhang, Chenmiao Zhang, Mingxi Fu, Zhongbo Li and 4 more

Abstract read
In one paragraph

Article in Cancer research, 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

14 authors.

Huijie Yang *Xinxiang Key Laboratory of Tumor Migration and Invasion Precision Medicine, School of Medical Technology, Xinxiang Medical University, Xinxiang, P.R. China.ORCID 0000-0002-6103-3979
Jiayao Cui *Xinxiang Key Laboratory of Tumor Migration and Invasion Precision Medicine, School of Medical Technology, Xinxiang Medical University, Xinxiang, P.R. China.ORCID 0009-0004-7740-1379
Peng Su *Department of Pathology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, P.R. China.ORCID 0000-0002-7000-0474
Xiujie Cui *Department of Pathology, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, P.R. China.ORCID 0009-0004-9143-6148
Haojie GuoDepartment of Ultrasound Medicine, the First Affiliated Hospital of Xinxiang Medical University, Xinxiang, P.R. China.ORCID 0009-0004-5447-2908
Penghe YangXinxiang Key Laboratory of Tumor Migration and Invasion Precision Medicine, School of Medical Technology, Xinxiang Medical University, Xinxiang, P.R. China.ORCID 0009-0007-3085-2174
Shuqing ZhangXinxiang Key Laboratory of Tumor Migration and Invasion Precision Medicine, School of Medical Technology, Xinxiang Medical University, Xinxiang, P.R. China.ORCID 0009-0000-0385-1749
Chenmiao ZhangXinxiang Key Laboratory of Tumor Migration and Invasion Precision Medicine, School of Medical Technology, Xinxiang Medical University, Xinxiang, P.R. China.ORCID 0009-0002-1658-762X
Mingxi FuXinxiang Key Laboratory of Tumor Migration and Invasion Precision Medicine, School of Medical Technology, Xinxiang Medical University, Xinxiang, P.R. China.ORCID 0009-0001-3559-5046
Zhongbo LiDepartment of General Surgery, Shengjing Hospital of China Medical University, Shenyang, P.R. China.ORCID 0009-0001-4840-3779
Yinlu DingDepartment of General Surgery, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, P.R. China.ORCID 0000-0001-8111-8964
Ting ZhuangXinxiang Key Laboratory of Tumor Migration and Invasion Precision Medicine, School of Medical Technology, Xinxiang Medical University, Xinxiang, P.R. China.ORCID 0000-0002-6308-1253
Jian ZhuDepartment of General Surgery, Shengjing Hospital of China Medical University, Shenyang, P.R. China.ORCID 0000-0003-3596-4339
Xiaodong TanDepartment of General Surgery, Shengjing Hospital of China Medical University, Shenyang, P.R. China.ORCID 0000-0003-0862-1306

Funding

Henan Province Science and Technology Innovation Talent Program () 242301420080Liaoning Revitalization Talents Program () XLYC2403044National Natural Science Foundation of China-Liaoning Joint Fund (-) 001National Natural Science Foundation of China-Liaoning Joint Fund (-) 005National Natural Science Foundation of China (NSFC) No. 82172999National Natural Science Foundation of China (NSFC) No. 82203507National Natural Science Foundation of China (NSFC) No.82372969Natural Science Foundation of Henan Province (Henan Natural Science Foundation) 222300420065Natural Science Foundation of Shandong Province () 222321MH017Science and Technology Innovation Talents in Universities of Henan Province () 21HASTIT049Taishan Scholar Project of Shandong Province tsqn202103175Taishan Scholar Project of Shandong Province tsqn202306365Zhongyuan University of Technology (ZUT)
6 · The paper itself

Abstract

Dysregulation of Hippo signaling, especially the downstream effector YAP, is a critical driver of hepatocellular carcinoma (HCC). Therefore, identifying therapeutic targets to block Hippo signaling could help improve survival outcomes for patients with HCC. In this study, we conducted an unbiased siRNA screen on G protein-coupled receptors targeted by drugs approved in the United States and strongly associated with the Hippo/YAP pathway and identified the oxytocin receptor (OXTR) as an important activator of the Hippo/YAP axis in HCC. The OXTR was correlated with the Hippo gene signature and poor survival outcomes in HCC, and OXTR activation promoted HCC progression through the Hippo/YAP axis. The OXTR antagonist atosiban blocked the growth of HCC in xenograft, patient-derived explant, organoid, and MST1/2 double-knockout mouse models. Molecular studies revealed that activation of the OXTR facilitated YAP dephosphorylation, nuclear accumulation, and transcriptional activation in HCC. OXTR interacted with Gαq/11 at several important sites (R137, I141, and I227) and induced YAP activation through the Gαq/11/Rho-associated protein kinase/LATS axis. Chromatin immunoprecipitation assays showed that YAP bound to the enhancer region of the OXTR and facilitated its transcription, creating a positive feedback loop. Together, this study uncovered the interplay between Hippo signaling and the OXTR pathway in hepatocarcinogenesis and established OXTR inhibition with atosiban as a promising strategy for treating HCC. SIGNIFICANCE: The FDA-approved oxytocin receptor antagonist atosiban can ameliorate Hippo signaling dysfunction in liver cancer to suppress tumor growth, providing an effective and rapidly translatable therapy for hepatocellular carcinoma.

Indexed as

Carcinoma, HepatocellularLiver NeoplasmsProtein Serine-Threonine KinasesReceptors, OxytocinTranscription FactorsAnimalsCarcinogenesisCell Cycle ProteinsCell Line, TumorCell ProliferationGene Expression Regulation, NeoplasticHippo Signaling PathwayHumansMiceMice, KnockoutMice, NudeCell Cycle ProteinsOXTR protein, humanProtein Serine-Threonine KinasesReceptors, OxytocinTranscription FactorsYAP1 protein, humanYAP-Signaling Proteins

Identifiers

PMID40742309
PMCPMC12485389

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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.