ArticleJournal of experimental & clinical cancer research : CR2019
β-Catenin nuclear localization positively feeds back on EGF/EGFR-attenuated AJAP1 expression in breast cancer.
Article in Journal of experimental & clinical cancer research : CR, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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17 citing papers in PubMed, 18 citations in OpenAlex.
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- Znhit1 and HIF-2α are correlated with cancer stem cell markers in breast cancer patients.Scientific reports · 2022Article
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- A novel prognostic model based on six methylation-driven genes predicts overall survival for patients with clear cell renal cell carcinoma.Frontiers in genetics · 2022Article
- Expression Patterns of Ezrin and AJAP1 and Clinical Significance in Breast Cancer.Frontiers in oncology · 2022Article
- Hypoxia-inducible miR-196a modulates glioblastoma cell proliferation and migration through complex regulation of NRAS.Cellular oncology (Dordrecht, Netherlands) · 2021Article
- Indonesian Ginger (Bangle) Extract Promotes Neurogenesis of Human Neural Stem Cells through WNT Pathway Activation.International journal of molecular sciences · 2020Article
- Downregulation of TET1 Promotes Bladder Cancer Cell Proliferation and Invasion by Reducing DNA Hydroxymethylation of AJAP1.Frontiers in oncology · 2020Article
- Extracellular vesicles expressing a single-chain variable fragment of an HIV-1 specific antibody selectively target EnvTheranostics · 2019Article
- TGF-β1 stimulates epithelial-mesenchymal transition and cancer-associated myoepithelial cell during the progression from in situ to invasive breast cancer.Cancer cell international · 2019Article
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundAdherent junction associated protein 1 (AJAP1), a typical molecule of adherent junctions, has been found to be a tumor suppressor in many cancer types. Aberrant activation of β-catenin has been demonstrated to be associated with malignant biological properties of tumors including breast cancer. This study aimed to investigate the function and mechanism of AJAP1-mediated β-catenin activity of breast cancer lines in vitro and in breast cancer patients.
methodsAJAP1 and β-catenin expressions in breast cancer tissues and cell lines were detected by immunohistochemistry, western blotting and qRT-PCR. The EGF/EGFR axis-mediated AJAP1 attenuated β-catenin nuclear location was measured by western blotting, immunofluorescence assay, co-immunoprecipitation, luciferase assay and ubiquitination assays. Furthermore, the function of AJAP1 and β-catenin regulated breast cancer progression was explored both in vivo and in vitro.
resultsIt was found that AJAP1 had a high negative correlation with β-catenin nuclear expression and was a novel tumor suppressor in breast cancer. AJAP1 loss can mediate β-catenin accumulated in cytoplasm and then transferred it to the nucleus, activating β-catenin transcriptional activity and downstream genes. Additionally, β-catenin can reverse the invasion, proliferation ability and tumorigenicity of the depletion of AJAP1 caused both in vivo and in vitro. Besides, EGF/EGFR also involved in the process of AJAP1-depiction induced β-catenin transactivation to the nucleus. More importantly, EGFR depletion/AJAP1 knocked down promoted the progression of breast cancer by regulating the activity of β-catenin nuclear transactivation.
conclusionThis study demonstrated that AJAP1 acted as a putative tumor suppressor while β-catenin nuclear localization positively fed back on EGF/EGFR-attenuated AJAP1 expression in breast cancer, which might be beneficial to develop new therapeutic targets for decreasing nuclear β-catenin-mediated malignancy in breast cancer.
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