Data from FOXP4 Is a Direct YAP1 Target That Promotes Gastric Cancer Stemness and Drives Metastasis Article Swipe
Xiaoli Liu
,
Bonan Chen
,
Fuda Xie
,
Kit Yee Wong
,
Alvin Ho‐Kwan Cheung
,
Jinglin Zhang
,
Qian Wu
,
Canbin Fang
,
Jintao Hu
,
Shouyu Wang
,
Dazhi Xu
,
Jianwu Chen
,
Yuzhi Wang
,
Chi Chun Wong
,
Huarong Chen
,
William Ka Kei Wu
,
Jun Yu
,
Michael W.Y. Chan
,
Chi Man Tsang
,
Kwok Wai Lo
,
Gary M. Tse
,
Ka‐Fai To
,
Wei Kang
·
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.1158/0008-5472.c.7523013
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.1158/0008-5472.c.7523013
The Hippo–YAP1 pathway is an evolutionally conserved signaling cascade that controls organ size and tissue regeneration. Dysregulation of Hippo–YAP1 signaling promotes initiation and progression of several types of cancer, including gastric cancer. As the Hippo–YAP1 pathway regulates expression of thousands of genes, it is important to establish which target genes contribute to the oncogenic program driven by YAP1 to identify strategies to circumvent it. In this study, we identified a vital role of forkhead box protein 4 (FOXP4) in YAP1-driven gastric carcinogenesis by maintaining stemness and promoting peritoneal metastasis. Loss of FOXP4 impaired gastric cancer spheroid formation and reduced stemness marker expression, whereas FOXP4 upregulation potentiated cancer cell stemness. RNA sequencing analysis revealed SOX12 as a downstream target of FOXP4, and functional studies established that SOX12 supports stemness in YAP1-induced carcinogenesis. A small-molecule screen identified 42-(2-tetrazolyl) rapamycin as a FOXP4 inhibitor, and targeting FOXP4 suppressed gastric cancer tumor growth and enhanced the efficacy of 5-fluorouracil chemotherapy in vivo. Collectively, these findings revealed that FOXP4 upregulation by YAP1 in gastric cancer regulates stemness and tumorigenesis by upregulating SOX12. Targeting the YAP1–FOXP4–SOX12 axis represents a potential therapeutic strategy for gastric cancer.Significance: Hippo–YAP1 signaling maintains stemness in gastric cancer by upregulating FOXP4, identifying FOXP4 as a stemness biomarker and therapeutic target that could help improve patient outcomes.
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Concepts
Metadata
- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.1158/0008-5472.c.7523013
- OA Status
- gold
- Cited By
- 1
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4404049184
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4404049184Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1158/0008-5472.c.7523013Digital Object Identifier
- Title
-
Data from FOXP4 Is a Direct YAP1 Target That Promotes Gastric Cancer Stemness and Drives MetastasisWork title
- Type
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preprintOpenAlex work type
- Language
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enPrimary language
- Publication year
-
2024Year of publication
- Publication date
-
2024-11-04Full publication date if available
- Authors
-
Xiaoli Liu, Bonan Chen, Fuda Xie, Kit Yee Wong, Alvin Ho‐Kwan Cheung, Jinglin Zhang, Qian Wu, Canbin Fang, Jintao Hu, Shouyu Wang, Dazhi Xu, Jianwu Chen, Yuzhi Wang, Chi Chun Wong, Huarong Chen, William Ka Kei Wu, Jun Yu, Michael W.Y. Chan, Chi Man Tsang, Kwok Wai Lo, Gary M. Tse, Ka‐Fai To, Wei KangList of authors in order
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https://doi.org/10.1158/0008-5472.c.7523013Publisher landing page
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YesWhether a free full text is available
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goldOpen access status per OpenAlex
- OA URL
-
https://doi.org/10.1158/0008-5472.c.7523013Direct OA link when available
- Concepts
-
Metastasis, YAP1, Cancer, Hippo signaling pathway, Medicine, Biology, Oncology, Cancer research, Internal medicine, Transcription factor, Genetics, Kinase, GeneTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
1Total citation count in OpenAlex
- Citations by year (recent)
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2025: 1Per-year citation counts (last 5 years)
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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