ArticleCell communication and signaling : CCS2023
WWP2 drives the progression of gastric cancer by facilitating the ubiquitination and degradation of LATS1 protein.
Article in Cell communication and signaling : CCS, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 31 citations in OpenAlex.
- WWP2 ubiquitin ligase promotes colorectal cancer progression by targeting p53 for degradation: an experimental study.Annals of surgical treatment and research · 2026Article
- WWP2 in immune surveillance and antigen presentation: context-dependent roles in B cells, T cells, and tumor immune escape.Frontiers in immunology · 2026Review
- Targeting ubiquitination in disease and therapy.Signal transduction and targeted therapy · 2025Review
- Targeting TIMM23 to overcome osteosarcoma chemoresistance.Cell death & disease · 2025Article
- UCHL3 depletion inhibits gastric cancer progression and enhances palbociclib sensitivity by regulating the AKT/CCND1 signaling axis via ENO1 ubiquitination.Cell death & disease · 2025Article
- TRIM47 Facilitates Osteosarcoma Progression via Destabilising FBP1 and Thus Activation of Wnt/β-Catenin Pathway.Journal of cellular and molecular medicine · 2025Article
- Pan-cancer analysis of oncogenic role of MAGOH and experiment validation in hepatocellular carcinoma.Scientific reports · 2025Article
- SNX5 facilitates the progression of gastric cancer by increasing the membrane localization of LRP5.Oncogene · 2025Article
- Single-cell multi-omics elucidates the role of RPS27-RPS24 fusion gene in osteosarcoma chemoresistance and metabolic regulation.Cell death discovery · 2025Article
- YAP/TAZ-Hippo pathway mediates the tumorigenesis of various cancers through post-translational modification represented by ubiquitination.Cell death discovery · 2025Article
- New insights into the role of ubiquitination in angiogenesis (Review).International journal of molecular medicine · 2025Review
- Implication of protein post translational modifications in gastric cancer.Frontiers in cell and developmental biology · 2025Review
- Hippo signaling pathway in cervical cancer: insights into mechanisms and therapeutic potential.Frontiers in oncology · 2025Review
- MLL1 promotes placental trophoblast ferroptosis and aggravates preeclampsia symptoms through epigenetic regulation of RBM15/TRIM72/ADAM9 axis.Biology direct · 2024Article
- SPIN1 accelerates tumorigenesis and confers radioresistance in non-small cell lung cancer by orchestrating the FOXO3a/FOXM1 axis.Cell death & disease · 2024Article
- CMTM5 influences Hippo/YAP axis to promote ferroptosis in glioma through regulating WWP2-mediated LATS2 ubiquitination.The Kaohsiung journal of medical sciences · 2024Article
- Article
- TMEM160 promotes tumor immune evasion and radiotherapy resistance via PD-L1 binding in colorectal cancer.Cell communication and signaling : CCS · 2024Article
- Lipid kinase PIP5Kα contributes to Hippo pathway activation via interaction with Merlin and by mediating plasma membrane targeting of LATS1.Cell communication and signaling : CCS · 2023Article
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Authors and funding
14 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundLarge tumor suppressor kinase 1 (LATS1), one of the predominant components of the Hippo pathway, has been characterized as a key player controlling the proliferation and invasion of cancer cells, including gastric cancer (GC) cells. However, the mechanism by which the functional stability of LATS1 is modulated has yet to be elucidated.
methodsOnline prediction tools, immunohistochemistry and western blotting assays were used to explore the expression of WW domain-containing E3 ubiquitin ligase 2 (WWP2) in GC cells and tissues. Gain- and loss-of-function assays, as well as rescue experiments were performed to determine the role of the WWP2-LATS1 axis in cell proliferation and invasion. Additionally, the mechanisms involving WWP2 and LATS1 were assessed by coimmunoprecipitation (Co-IP), immunofluorescence, cycloheximide and in vivo ubiquitination assays.
resultsOur results demonstrate a specific interaction between LATS1 and WWP2. WWP2 was markedly upregulated and correlated with disease progression and a poor prognosis in GC patients. Moreover, ectopic WWP2 expression facilitated the proliferation, migration and invasion of GC cells. Mechanistically, WWP2 interacts with LATS1, resulting in its ubiquitination and subsequent degradation, leading to increased transcriptional activity of YAP1. Importantly, LATS1 depletion abolished the suppressive effects of WWP2 knockdown on GC cells. Furthermore, WWP2 silencing attenuated tumor growth by regulating the Hippo-YAP1 pathway in vivo.
conclusionsOur results define the WWP2-LATS1 axis as a critical regulatory mechanism of the Hippo-YAP1 pathway that promotes GC development and progression. Video Abstract.
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