Evidence mapPaperPMID 41350729Full record

ArticleJournal of translational medicine2025

FAM189A2 activates Hippo signaling pathway by abrogating WWP2-mediated LATS1 ubiquitination, to inhibit the glycolysis and proliferation processes of lung adenocarcinoma.

Bingyu Chen, Xuezhu Rong, Yuheng Feng, Yuekang Hou, Lin Fu, Qiang Han, Yan Song, Xuyong Lin

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Article in Journal of translational medicine, 2025. 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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4 · The record

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5 · Who and what money

Authors and funding

8 authors.

Bingyu Chen *Department of Pathology, The First Hospital and College of Basic Medical Sciences of China Medical University, Shenyang, China.
Xuezhu Rong *Department of Pathology, The First Hospital and College of Basic Medical Sciences of China Medical University, Shenyang, China.
Yuheng FengDepartment of Pathology, The First Hospital and College of Basic Medical Sciences of China Medical University, Shenyang, China.
Yuekang HouDepartment of Pathology, The First Hospital and College of Basic Medical Sciences of China Medical University, Shenyang, China.
Lin FuDepartment of Pathology, The First Hospital and College of Basic Medical Sciences of China Medical University, Shenyang, China.
Qiang HanDepartment of Pathology, The First Hospital and College of Basic Medical Sciences of China Medical University, Shenyang, China. qhan@cmu.edu.cn.
Yan SongDepartment of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17, Nanli, Panjiayuan, Chaoyang District, Beijing, 100021, PR China. songyan@cicams.ac.cn.
Xuyong LinDepartment of Pathology, The First Hospital and College of Basic Medical Sciences of China Medical University, Shenyang, China. linxuyong@hotmail.com.

Funding

National Natural Science Foundation of China 81902986National Natural Science Foundation of China 82003119Natural Science Foundation of Liaoning Province 2022-MS-198
6 · The paper itself

Abstract

backgroundMetabolic abnormalities have become a prominent hallmark of malignant tumor and play a crucial role in the occurrence and development of lung adenocarcinoma (LUAD). however, the underlying mechanism involved this process is still far from being fully elucidated. In this study, we aimed to explore the essential factors regulating the glycolysis and proliferation process in LUAD.

methodsBioinformation and immunohistochemistry were applied to screen and verify the expression pattern of the vital factors in LUAD. A series of biological function assays, including Cell Counting Kit 8 (CCK8), colony formation, 5-ethynyl-2'-deoxyuridine‌ (EdU), seahorse assays and nude mouse transplantation tumor assays, were performed to demonstrate the impact of the family with sequence similarity 189 member A2 (FAM189A2) on the glycolysis and proliferation process in LUAD. Co-immunoprecipitation, immunofluorescence and dual-luciferase reporter gene and RT-qPCR were used to verify the FAM129A2 and the WW domains of E3 ubiquitin ligase (WWP2) interaction, as well as the influence of their combination on large tumour suppressor-1 (LATS1) ubiquitination level and Hippo signaling pathway activity.

resultsFAM189A2 was weakly expressed in the cytoplasm of LUAD, and associated with the poor prognosis of patients. FAM189A2 overexpression inhibited the glycolysis and proliferation processes of LUAD cells in vitro. Meanwhile, both the processes were enhanced following FAM189A2 knockdown. Mechanistically, FAM189A2 was identified to interact with WWP2 through its own PPxY motifs, hence weakened the WWP2-LATS1 affinity and inhibited the WWP2-mediated LATS1 ubiquitination, which ultimately resulted in a reduced yes-associated protein (YAP) nuclear translocation. In addition, Verteporfin (Hippo pathway inhibitor) or YAP knockdown could eliminate the biological effects of promoting proliferation and glycolysis in LUAD cells caused by FAM189A1 silence.

conclusionsFAM189A2 can be considered as a potential diagnostic and prognostic marker associated with LUAD, and suppresses the proliferation and glycolytic metabolism of LUAD cells via WWP2-LATS1-YAP signaling, which will provide a corresponding theoretical foundation for the development of small molecule inhibitors.

Indexed as

Adenocarcinoma of LungGlycolysisHippo Signaling PathwayLung NeoplasmsProtein Serine-Threonine KinasesSignal TransductionUbiquitinationUbiquitin-Protein LigasesAnimalsCell Line, TumorCell ProliferationFemaleHumansMaleMiceMice, NudeLATS1 protein, humanProtein Serine-Threonine KinasesUbiquitin-Protein LigasesFAM189A2GlycolysisHippo signaling pathwayLATS1Lung adenocarcinomaUbiquitinationWWP2

Identifiers

PMID41350729
PMCPMC12797836

What Socratic holds

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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 Socratic graph.