ArticleJournal of experimental & clinical cancer research : CR2019
Elevated expression of Gab1 promotes breast cancer metastasis by dissociating the PAR complex.
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 18 papers.
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Who cites it
18 citing papers in PubMed, 24 citations in OpenAlex.
- circGAB1 Activates Autophagy to Promote Sepsis-Associated Acute Kidney Injury by Interacting with ELAVL1 to Activate the HMGB3/β-catenin Signaling Pathway.Applied biochemistry and biotechnology · 2026Article
- ShcD adaptor protein drives invasion of triple negative breast cancer cells by aberrant activation of EGFR signaling.Molecular oncology · 2025Article
- Silencing of PIGU inhibits the progression of esophageal squamous cell carcinoma through the PI3K/AKT signaling pathway.Scientific reports · 2025Article
- Comprehensive molecular characteristics of hepatocellular carcinoma based on multi-omics analysis.BMC cancer · 2025Article
- Gab1 in Cardiovascular Disease: An Insufficiently Explored and Controversial Research Area.Cardiovascular drugs and therapy · 2025Article
- Dysregulated Gab1 signalling in triple negative breast cancer.Cell communication and signaling : CCS · 2024Article
- The Role of GAB1 in Cancer.Cancers · 2023Review
- Circ_0057452 sponges miR-7-5p to promote keloid progression through upregulating GAB1.Cell cycle (Georgetown, Tex.) · 2022Article
- LncRNA DLEU1 facilitates the progression of oral squamous cell carcinoma by miR-126-5p/GAB1 axis.The Kaohsiung journal of medical sciences · 2022Article
- Her2/EGFR-PDGFR pathway aberrations associated with tamoxifen response in metastatic breast cancer patients.Journal of the Egyptian National Cancer Institute · 2022Article
- MicroRNA-383: A tumor suppressor miRNA in human cancer.Frontiers in cell and developmental biology · 2022Review
- Dual Function of Par3 in Tumorigenesis.Frontiers in oncology · 2022Review
- Association of Single-Nucleotide Polymorphisms of Gab1 Gene with Susceptibility to Meningioma in a Northern Chinese Han Population.Medical science monitor : international medical journal of experimental and clinical research · 2021Article
- MiR-106b-5p: A Master Regulator of Potential Biomarkers for Breast Cancer Aggressiveness and Prognosis.International journal of molecular sciences · 2021Article
- GAB2 and GAB3 are expressed in a tumor stage-, grade- and histotype-dependent manner and are associated with shorter progression-free survival in ovarian cancer.Journal of cell communication and signaling · 2021Article
- Oncogenic circDHTKD1 promotes tumor growth and metastasis of oral squamous cell carcinoma in vitro and in vivo via upregulating miR-326-mediated GAB1.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2021Article
- In silico identification of the prognostic biomarkers and therapeutic targets associated with cancer stem cell characteristics of glioma.Bioscience reports · 2020Article
- KCancers · 2019Article
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundBreast cancer (BCa) remains as the second leading cause of cancer-related death in women worldwide. The majority of the deaths are due to its progression to metastatic BCa. Although Grb2-associated binding protein 1 (Gab1) has been implicated in tumor proliferation and metastasis in multiple tumors including colorectal cancer, hepatocellular carcinoma and ovarian cancer, whether and how it regulates BCa metastasis are still poorly understood.
methodsWestern blot assay and immunohistochemical (IHC) staining were performed to assess expression of Gab1 in primary and metastatic BCa clinical samples. Biological function assay studies in vitro and in vivo were employed to investigate the functions of Gab1 during BCa metastasis. Co-immunoprecipitation (co-IP) assessment, western blot assay and immunofluorescence (IF) staining were carried out to investigate the underlying mechanism for the function of Gab1 on BCa metastasis.
resultsIn this study, we found that expression level of Gab1 was increased significantly in BCa tissue samples compared to that in benign mammary hyperplastic tissues. Furthermore, elevated expression of Gab1 was positively associated with metastasis in HER2 and TNBC subtypes of BCa. In BCa cell line MDA-MB-231 and SK-BR3 cells, stable overexpression of Gab1 promoted, while knockdown of Gab1 inhibited cell migration in vitro and metastasis in vivo. Mechanistically, overexpression of Gab1 enhanced its interaction with Par3, a key component of the polarity-associated partitioning defective (PAR) complex, leading to a dissociation of the PAR complex. Consequently, dissociated PAR complex induced epithelial-to-mesenchymal transition (EMT) for breast tumor metastasis. By restoration assessment, we found that only re-expression of a fully functional Gab1, but not a mutant Gab1 that harbors either Par3 binding-deficiency or Par1b binding-deficiency, could reverse the repressive phenotype of cell migration in vitro and metastasis in vivo due to Gab1 knockdown.
conclusionsOur findings indicate that elevated expression of Gab1 promotes BCa metastasis by dissociating the PAR complex that leads to EMT, implicating a role of Gab1 as a potential biomarker of metastatic BCa. Moreover, inhibition of Gab1 expression might be a promising therapeutic strategy for BCa metastasis.
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