ArticleJournal of cellular and molecular medicine2017
WWC2 is an independent prognostic factor and prevents invasion via Hippo signalling in hepatocellular carcinoma.
Article in Journal of cellular and molecular medicine, 2017. 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, 30 citations in OpenAlex.
- Upregulation of miR-589-3p Contributes to Lung Adenocarcinoma Progression Through Inhibition of WWC2.Cancers · 2026Article
- WWC proteins as emerging biomarkers and therapeutic targets in cancer pathogenesis.Frontiers in cell and developmental biology · 2026Review
- m6A-modified circXPO1 accelerates colorectal cancer progression via interaction with FMRP to promote WWC2 mRNA decay.Journal of translational medicine · 2024Article
- Targeting the Hippo/YAP1 signaling pathway in hepatocellular carcinoma: From mechanisms to therapeutic drugs (Review).International journal of oncology · 2024Review
- Hippo pathway in non-small cell lung cancer: mechanisms, potential targets, and biomarkers.Cancer gene therapy · 2024Review
- The deadly cross-talk between Hippo pathway and epithelial-mesenchymal transition (EMT) in cancer.Molecular biology reports · 2022Review
- Identification of healthspan-promoting genes in Caenorhabditis elegans based on a human GWAS study.Biogerontology · 2022Article
- Long non-coding RNAs as the critical regulators of epithelial mesenchymal transition in colorectal tumor cells: an overview.Cancer cell international · 2022Review
- Advances in prognostic and therapeutic targets for hepatocellular carcinoma and intrahepatic cholangiocarcinoma: The hippo signaling pathway.Frontiers in oncology · 2022Review
- Cervical Cancer Cells-Derived Extracellular Vesicles Containing microRNA-146a-5p Affect Actin Dynamics to Promote Cervical Cancer Metastasis by Activating the Hippo-YAP Signaling PathwayJournal of oncology · 2022Article
- Inhibin βA is an independent prognostic factor that promotes invasion via Hippo signaling in non‑small cell lung cancer.Molecular medicine reports · 2021Article
- Transcriptional Modulation of the Hippo Signaling Pathway by Drugs Used to Treat Bipolar Disorder and Schizophrenia.International journal of molecular sciences · 2021Article
- Review
- The Crosstalk between Src and Hippo/YAP Signaling Pathways in Non-Small Cell Lung Cancer (NSCLC).Cancers · 2020Review
- Down-Regulation of LINC00460 Represses Metastasis of Colorectal Cancer via WWC2.Digestive diseases and sciences · 2020Article
- miR-21-5p promotes lung adenocarcinoma cell proliferation, migration and invasion via targeting WWC2.Cancer biomarkers : section A of Disease markers · 2020Observational
- Article
- The Role of Yes-Associated Protein (YAP) in Regulating Programmed Death-Ligand 1 (PD-L1) in Thoracic Cancer.Biomedicines · 2018Review
- Loss of KIBRA function activates EGFR signaling by inducing AREG.Oncotarget · 2018Article
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
WWC family proteins negatively regulate HEK293 cell proliferation and organ growth by suppressing the transcriptional activity of Yes-associated protein (YAP), a major effector of the Hippo pathway. The function of the scaffolding protein WWC1 (also called KIBRA) has been intensively studied in cells and animal models. However, the expression and clinicopathologic significance of WWC2 in cancer are poorly characterized. This study aimed to clarify the biological function and mechanism of action of WWC2 in hepatocellular carcinoma (HCC). Retrospective analysis revealed WWC2 was significantly down-regulated in 95 clinical HCC tissues compared to the paired adjacent non-cancerous tissues. Moreover, loss of WWC2 expression was significantly associated with advanced clinicopathological features, including venous infiltration, larger tumour size and advanced TNM stage. Positive WWC2 expression was associated with significantly better 5-year overall survival, and WWC2 was an independent prognostic factor for overall survival in HCC. Moreover, we confirmed WWC2 inhibits HCC cell invasive ability in vitro. Elevated YAP expression was also observed in the same cohort of HCC tissues. Pearson's correlation coefficient analysis indicated WWC2 expression correlated inversely with nuclear YAP protein expression in HCC. Mechanistically, we confirmed overexpression of WWC2 suppresses the invasive and metastatic potential of HCC cells by activating large tumour suppressor 1 and 2 kinases (LATS1/2), which in turn phosphorylates the transcriptional co-activator YAP. Overall, this study indicates WWC2 functions as a tumour suppressor by negatively regulating the Hippo signalling pathway and may serve as a prognostic marker in HCC.
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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 OpenQuestion graph.