ArticleOncogene2016
Overexpression of GAB2 in ovarian cancer cells promotes tumor growth and angiogenesis by upregulating chemokine expression.
Article in Oncogene, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 62 citations in OpenAlex.
- Chemokine-chemokine receptor axis: Emerging immunotherapeutic paradigms for solid tumor microenvironment reprogramming.Chinese medical journal · 2026Review
- The Significance of CXCL1 in Cancer: An Overview of Molecular Mechanisms.International journal of molecular sciences · 2026Review
- Integrated Molecular and Functional Characterization of Cervical Small-Cell Neuroendocrine Carcinoma Using a 3D Organoid Model.International journal of molecular sciences · 2026Article
- Direct Targeting of CXCR2 Receptor Inhibits Neuroblastoma Growth: An In Vitro Assessment.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Egfl6 promotes ovarian cancer progression by enhancing the immunosuppressive functions of tumor-associated myeloid cells.The Journal of clinical investigation · 2024Article
- An analysis of the role of GAB2 in pan-cancer from a multidimensional perspective.Discover oncology · 2024Article
- Recent Updates on Oncogenic Signaling of Aurora Kinases in Chemosensitive, Chemoresistant Cancers: Novel Medicinal Chemistry Approaches for Targeting Aurora Kinases.Current medicinal chemistry · 2024Review
- Gab2 promotes the growth of colorectal cancer by regulating the M2 polarization of tumor‑associated macrophages.International journal of molecular medicine · 2024Article
- CXCL8 Promotes Endothelial-to-Mesenchymal Transition of Endothelial Cells and Protects Cells from Erastin-Induced Ferroptosis via CXCR2-Mediated Activation of the NF-κB Signaling Pathway.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Review
- Involvement in Tumorigenesis and Clinical Significance of CXCL1 in Reproductive Cancers: Breast Cancer, Cervical Cancer, Endometrial Cancer, Ovarian Cancer and Prostate Cancer.International journal of molecular sciences · 2023Review
- Comprehensive bioinformatic analysis constructs a CXCL model for predicting survival and immunotherapy effectiveness in ovarian cancer.Frontiers in pharmacology · 2023Article
- Analysis of CXCL8 and its receptors CXCR1/CXCR2 at the mRNA level in neoplastic tissue, as well as in serum and peritoneal fluid in patients with ovarian cance.Molecular medicine reports · 2022Article
- Harnessing the chemokine system to home CAR-T cells into solid tumors.Cell reports. Medicine · 2022Review
- CXC Chemokine Signaling in Progression of Epithelial Ovarian Cancer: Theranostic Perspectives.International journal of molecular sciences · 2022Review
- 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
- Vascular Normalization: A New Window Opened for Cancer Therapies.Frontiers in oncology · 2021Review
- Mechanism underlying the regulation of lncRNA ACTA2-AS1 on CXCL2 by absorbing miRNA-532-5p as ceRNA in the development of ovarian cancer.International journal of clinical and experimental pathology · 2021Article
- Oncogenes in high grade serous adenocarcinoma of the ovary.Genes & cancer · 2020Article
- PIM Kinase Inhibitors Block the Growth of Primary T-cell Acute Lymphoblastic Leukemia: Resistance Pathways Identified by Network Modeling Analysis.Molecular cancer therapeutics · 2020Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
We previously found that the scaffold adapter GRB2-associated binding protein 2 (GAB2) is amplified and overexpressed in a subset of primary high-grade serous ovarian cancers and cell lines. Ovarian cancer cells overexpressing GAB2 are dependent on GAB2 for activation of the phosphatidylinositol 3-kinase (PI3K) pathway and are sensitive to PI3K inhibition. In this study, we show an important role of GAB2 overexpression in promoting tumor angiogenesis by upregulating expression of multiple chemokines. Specifically, we found that suppression of GAB2 by inducible small hairpin RNA in ovarian cancer cells inhibited tumor cell proliferation, angiogenesis and peritoneal tumor growth in immunodeficient mice. Overexpression of GAB2 upregulated the secretion of several chemokines from ovarian cancer cells, including CXCL1, CXCL2 and CXCL8. The secreted chemokines not only signal through endothelial CXCR2 receptor in a paracrine manner to promote endothelial tube formation, but also act as autocrine growth factors for GAB2-induced transformation of fallopian tube secretory epithelial cells and clonogenic growth of ovarian cancer cells overexpressing GAB2. Pharmacological inhibition of inhibitor of nuclear factor kappa-B kinase subunit β (IKKβ), but not PI3K, mechanistic target of rapamycin (mTOR) or mitogen-activated protein kinase (MEK), could effectively suppress GAB2-induced chemokine expression. Inhibition of IKKβ augmented the efficacy of PI3K/mTOR inhibition in suppressing clonogenic growth of ovarian cancer cells with GAB2 overexpression. Taken together, these findings suggest that overexpression of GAB2 in ovarian cancer cells promotes tumor growth and angiogenesis by upregulating expression of CXCL1, CXCL2 and CXCL8 that is IKKβ-dependent. Co-targeting IKKβ and PI3K pathways downstream of GAB2 might be a promising therapeutic strategy for ovarian cancer that overexpresses GAB2.
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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.