Evidence map›Paper›PMID 41981454›Full record

ArticleBiology direct2026

The MST4-14-3-3ζ complex promotes pancreatic cancer by activating YAP.

Luyang Tian, Zhangting Zhao, Shisi Ding, Mingquan Li, Yi Han, Chunxiao Zhu, Yu Pan, Xiaowei Wang, Wei Kang, Liwei An and 2 more

Abstract read
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In one paragraph

Article in Biology direct, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

12 authors.

Luyang TianState Key Laboratory of Genetics and Development of Complex Phenotypes, School of Life Sciences, Zhongshan Hospital, Fudan University, Shanghai, China.
Zhangting ZhaoDepartment of Stomatology, Department of Medical Ultrasound, Shanghai Tenth People's Hospital, School of Medicine, Tongji University Cancer Center, Tongji University, Shanghai, China.
Shisi DingDepartment of Stomatology, Department of Medical Ultrasound, Shanghai Tenth People's Hospital, School of Medicine, Tongji University Cancer Center, Tongji University, Shanghai, China.
Mingquan LiState Key Laboratory of Genetics and Development of Complex Phenotypes, School of Life Sciences, Zhongshan Hospital, Fudan University, Shanghai, China.
Yi HanDepartment of Stomatology, Department of Medical Ultrasound, Shanghai Tenth People's Hospital, School of Medicine, Tongji University Cancer Center, Tongji University, Shanghai, China.
Chunxiao ZhuState Key Laboratory of Genetics and Development of Complex Phenotypes, School of Life Sciences, Zhongshan Hospital, Fudan University, Shanghai, China.
Yu PanState Key Laboratory of Genetics and Development of Complex Phenotypes, School of Life Sciences, Zhongshan Hospital, Fudan University, Shanghai, China.
Xiaowei WangDepartment of Stomatology, Department of Medical Ultrasound, Shanghai Tenth People's Hospital, School of Medicine, Tongji University Cancer Center, Tongji University, Shanghai, China.
Wei KangDepartment of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, State Key Laboratory of Digestive Disease, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China.
Liwei AnDepartment of Stomatology, Department of Medical Ultrasound, Shanghai Tenth People's Hospital, School of Medicine, Tongji University Cancer Center, Tongji University, Shanghai, China.
Zhaocai ZhouState Key Laboratory of Genetics and Development of Complex Phenotypes, School of Life Sciences, Zhongshan Hospital, Fudan University, Shanghai, China. zhouzhaocai@fudan.edu.cn.
Yang TangDepartment of Stomatology, Department of Medical Ultrasound, Shanghai Tenth People's Hospital, School of Medicine, Tongji University Cancer Center, Tongji University, Shanghai, China. tangyang@tongji.edu.cn.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe mammalian STE20-like kinase 4 (MST4) has been implicated as a potential oncogene in various cancers, including pancreatic cancer (PC). However, the precise mechanisms through which MST4 promotes PC malignancy remain incompletely understood.

methodsA Biotin identification (BioID)-based proximity labeling approach was employed to identify key MST4-interacting molecules in human PANC-1 pancreatic cancer (PC) cells, followed by cell migration assay to validate the synergistic promotional effect of the MST4-interacting complex on PC cell migration. Direct binding between MST4 and its interacting partners was confirmed via microscale thermophoresis (MST) and isothermal titration calorimetry (ITC), with further validation through X-ray crystallographic structural analysis. The efficacy of rationally designed peptides targeting this interaction was evaluated in both in vitro cell models and in vivo xenograft mouse models.

resultsIn this study, we demonstrate that MST4 forms a phosphorylation-dependent complex with 14-3-3ζ, leading to Yes-associated protein (YAP) activation and synergistic enhancement of PC cell migration. We observed significant upregulation of both MST4 and 14-3-3ζ in PC patient samples, which correlated strongly with YAP activation and poor prognosis. Structural analysis revealed the detailed interface of the MST4–14-3-3ζ complex, facilitating the rational design of peptide inhibitors that disrupt this interaction. These peptides effectively suppressed YAP activation and exhibited potent anti-tumor effects both in vitro and in vivo.

conclusionsOur findings establish the MST4–14-3-3ζ complex as a critical regulator of YAP signaling that synergistically promotes PC cell migration. Furthermore, rationally designed peptides targeting this MST4–14-3-3ζ interaction represent a promising therapeutic strategy for pancreatic cancer and warrant further clinical exploration.

Indexed as

14-3-3 ProteinsAdaptor Proteins, Signal TransducingPancreatic NeoplasmsProtein Serine-Threonine KinasesTranscription FactorsAnimalsCell Cycle ProteinsCell Line, TumorCell MovementHippo KinasesHumansIntracellular Signaling Peptides and ProteinsMicePhosphorylationYAP-Signaling Proteins14-3-3 ProteinsAdaptor Proteins, Signal TransducingCell Cycle ProteinsHippo KinasesIntracellular Signaling Peptides and ProteinsProtein Serine-Threonine KinasesSTK4 protein, humanTranscription FactorsYAP1 protein, humanYAP-Signaling ProteinsMST4–14-3-3ζ complexPancreatic cancerPeptide inhibitorsTargeted therapyYAP-Hippo pathway

Identifiers

PMID41981454
PMCPMC13191904

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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.