The long noncoding RNA ELFN1-AS1 promotes gastric cancer growth and metastasis by interacting with TAOK1 to inhibit the Hippo signaling pathway
Gastric cancer (GC) is a common digestive malignancy that causes numerous cancer-related deaths. Long noncoding RNAs (lncRNAs) play a crucial role in the development of various tumors, including GC. In this study, we revealed that ELFN1-AS1, a lncRNA with aberrantly high expression, contributes to the proliferation and metastasis of GC. Mechanically, ELFN1-AS1 plays an oncogenic role by binding to the protein kinase domain of thousand and one amino acid protein kinase (TAOK1), a tumor suppressor in GC, and disrupting the TAOK1-STK3 interaction, leading to decreased STK3 phosphorylation. This decrease is accompanied by attenuation of the Hippo kinase cascade, resulting in reduced YAP1 phosphorylation, a crucial effector of the Hippo signaling pathway. Subsequently, the reduced YAP1 phosphorylation promotes its nuclear translocation, thereby enhancing the expression of MYC, a downstream target of the pathway and well-known oncogene. Taken together, the ELFN1-AS1/TAOK1/STK3/YAP1 axis may promote GC progression and is a promising target for GC treatment.
Authors
- Jason Chia‐Hsien Cheng (ORCID: https://orcid.org/0000-0002-2007-0220)
- Xinyi Zhou (ORCID: https://orcid.org/0000-0002-2862-7476)
- Kanghui Liu (ORCID: https://orcid.org/0009-0009-4712-7774)
- Kuan Shen
- Li Hu (ORCID: https://orcid.org/0000-0002-7535-6453)
- Jian Xiao (ORCID: https://orcid.org/0000-0002-8825-8385)
- Yuanhang Wang (ORCID: https://orcid.org/0009-0006-0535-4686)
Institutions
- Yancheng Third People's Hospital (CN)
- Jiangsu Province Hospital (CN)
- Nanjing Medical University (CN)
Publication Details
- Journal
- Cell Death Discovery
- Published
- 2024-11-11
- DOI
- https://doi.org/10.1038/s41420-024-02235-5
- Citations
- 3
- Primary Topic
- Cancer-related molecular mechanisms research
- Type
- article
- Field-Weighted Citation Impact
- 0.86