ArticleCell death discovery2022
The E3 ubiquitin ligase, FBXW5, promotes the migration and invasion of gastric cancer through the dysregulation of the Hippo pathway.
Article in Cell death discovery, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 40 citations in OpenAlex.
- Gemcitabine activates the Hippo signaling pathway and suppresses tumor growth by stabilizing large tumor suppressor kinase 2 through the hypoxia-inducible factor 1-alpha/ubiquitin protein ligase E3 component N-recognin 5 axis.Journal of cell communication and signaling · 2026Article
- Targeting ubiquitination in disease and therapy.Signal transduction and targeted therapy · 2025Review
- The structure and function of FBXW5 in human diseases.Biochemistry and biophysics reports · 2025Review
- Construction and validation of a post-translational modification-related signature to predict the effect of immune therapies in gastric cancer.Biochemistry and biophysics reports · 2025Article
- FOXP2 suppresses gastric cancer progression by transcriptionally repressing FBXW2 via WASL degradation.Cell death discovery · 2025Article
- TMEM160 inhibits KEAP1 to suppress ferroptosis and induce chemoresistance in gastric cancer.Cell death & disease · 2025Article
- Article
- Individual disruption of 12 testis-enriched genes via the CRISPR/Cas9 system does not affect the fertility of male mice.Journal of reproductive immunology · 2024Article
- YAP1-CPNE3 positive feedback pathway promotes gastric cancer cell progression.Cellular and molecular life sciences : CMLS · 2024Article
- Isoform alterations in the ubiquitination machinery impacting gastrointestinal malignancies.Cell death & disease · 2024Review
- TMEM160 promotes tumor immune evasion and radiotherapy resistance via PD-L1 binding in colorectal cancer.Cell communication and signaling : CCS · 2024Article
- GPR137 inactivates Hippo signaling to promote gastric cancer cell malignancy.Biology direct · 2024Article
- DPP2/7 is a Potential Predictor of Prognosis and Target in Immunotherapy in Colorectal Cancer: An Integrative Multi-omics Analysis.Combinatorial chemistry & high throughput screening · 2024Article
- F-box proteins and gastric cancer: an update from functional and regulatory mechanism to therapeutic clinical prospects.International journal of medical sciences · 2024Review
- Review
- Function, mechanism and drug discovery of ubiquitin and ubiquitin-like modification with multiomics profiling for cancer therapy.Acta pharmaceutica Sinica. B · 2023Review
- Targeting XPO6 inhibits prostate cancer progression and enhances the suppressive efficacy of docetaxel.Discover oncology · 2023Article
- The Hippo signaling pathway in gastric cancer.Acta biochimica et biophysica Sinica · 2023Review
- Upregulated GPRC5A disrupting the Hippo pathway promotes the proliferation and migration of pancreatic cancer cells via the cAMP-CREB axis.Discover oncology · 2023Article
- UPS: Opportunities and challenges for gastric cancer treatment.Frontiers in oncology · 2023Review
Corrections and comments
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Authors and funding
16 authors at 2 institutions in 1 country.
Funding
Abstract
F-box and WD repeat domain-containing 5 (FBXW5), with WD40 repeats, can bind to the PPxY sequence of the large tumor suppressor kinases 1/2 (LATS1/2) kinase domain, resulting in ubiquitination. Ubiquitination and the subsequent degradation of LATS1/2 abrogate the Hippo pathway and worsen gastric cancer (GC). However, the effects and molecular mechanisms of FBXW5 in GC remain unexplored. To elucidate the clinical significance of FBXW5, immunohistochemistry was conducted to reveal the positive correlation between FBXW5 expression and lymph node metastasis (p < 0.001) and TNM stage (training cohort: p = 0.018; validation cohort: p = 0.001). Further, patients with high FBXW5 expression were found to have poor prognosis (training cohort: log-rank p = 0.020; validation cohort: log-rank p = 0.025). Cell experiments revealed the promoting effects of FBXW5 on the proliferation, invasion, metastasis, and chemoresistance of GC cells. Blocking LATS1-YAP1 leads to the loss of FBXW5-mediated regulation of the Hippo pathway and partial functions. Further, co-immunoprecipitation and in vivo ubiquitination assays revealed the interaction between FBXW5 and LATS1, which promoted the ubiquitination and degradation of LATS1. Based on mouse xenograft assays, FBXW5 silencing attenuated the growth of subcutaneous tumor xenografts. Altogether, FBXW5 was found to inactivate the Hippo signaling pathway by enhancing LATS1 ubiquitination and degradation, which promoted the invasion, metastasis, and drug resistance of GC cells.
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Registered trials
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.