ArticleCancer2019
The role of vascular endothelial growth factor, interleukin 8, and insulinlike growth factor in sustaining autophagic DIRAS3-induced dormant ovarian cancer xenografts.
Article in Cancer, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 31 citations in OpenAlex.
- The sleeping threat: targeting cancer dormancy to transform metastasis therapy.Nature reviews. Cancer · 2026Review
- Cross-talk between cancer-associated fibroblasts and dormant cancer cells: current status and promising therapeutic potential.Cancer cell international · 2025Review
- Dormant cancer cells and polyploid giant cancer cells: The roots of cancer recurrence and metastasis.Clinical and translational medicine · 2024Review
- Dormancy, stemness, and therapy resistance: interconnected players in cancer evolution.Cancer metastasis reviews · 2023Review
- Autophagy, molecular chaperones, and unfolded protein response as promoters of tumor recurrence.Cancer metastasis reviews · 2023Review
- AMPK-mTOR-Mediated Activation of Autophagy Promotes Formation of Dormant Polyploid Giant Cancer Cells.Cancer research · 2022Article
- Review
- DIRAS2 Is a Prognostic Biomarker and Linked With Immune Infiltrates in Melanoma.Frontiers in oncology · 2022Article
- Activation of SphK2 contributes to adipocyte-induced EOC cell proliferation.Open medicine (Warsaw, Poland) · 2022Article
- Cancer Immunoediting: Elimination, Equilibrium, and Immune Escape in Solid Tumors.Experientia supplementum (2012) · 2022Article
- Novel Anti-Angiogenic and Anti-Tumour Activities of the N-Terminal Domain of NOEY2 via Binding to VEGFR-2 in Ovarian Cancer.Biomolecules & therapeutics · 2021Article
- Interleukin‑8 released by cancer‑associated fibroblasts attenuates the autophagy and promotes the migration of ovarian cancer cells.International journal of oncology · 2021Article
- Fibroblasts in cancer dormancy: foe or friend?Cancer cell international · 2021Review
- Autophagy and Cancer Dormancy.Frontiers in oncology · 2021Review
- Article
- CXCL8 is a potential biomarker for predicting disease progression in gastric carcinoma.Translational cancer research · 2020Article
- Antiangiogenesis Efficacy of Ethanol Extract fromEvidence-based complementary and alternative medicine : eCAM · 2020Article
- Review
- Article
- miR-139 Controls Viability Of Ovarian Cancer Cells Through Apoptosis Induction And Exosome Shedding Inhibition By Targeting ATP7A.OncoTargets and therapy · 2019Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
backgroundRe-expression of the imprinted tumor suppressor gene DIRAS family GTPase 3 (DIRAS3) (aplysia ras homology member I [ARHI]) induces autophagy and tumor dormancy in ovarian cancer xenografts, but drives autophagic cancer cell death in cell culture. The current study explored the tumor and host factors required to prevent autophagic cancer cell death in xenografts and the use of antibodies against those factors or their receptors to eliminate dormant autophagic ovarian cancer cells.
methodsSurvival factors (insulinlike growth factor 1 [IGF-1], vascular endothelial growth factor [VEGF], and interleukin 8 [IL-8]) were detected with growth factor arrays and measured using enzyme-linked immunoadsorbent assay analysis. Phosphorylation of protein kinase B (AKT), phosphorylation of extracellular signal-regulated kinase (ERK), nuclear localization of translocation factor EB (TFEB) or forkhead box O3a (FOXo3a), and expression of microtubule-associated proteins 1A/1B light chain 3B (MAPLC3B; LC3B) were examined using Western blot analysis. The effect of treatment with antibodies against survival factors or their receptors was studied using DIRAS3-induced dormant xenograft models.
resultsOvarian cancer cells grown subcutaneously in nude mice exhibited higher levels of phosphorylated ERK/AKT activity and lower levels of nuclear TFEB/FOXo3a, MAPLC3B, and autophagy compared with cells grown in culture. Induction of autophagy and dormancy with DIRAS3 was associated with decreased ERK/AKT signaling. The addition of VEGF, IGF-1, and IL-8 weakened the inhibitory effect of DIRAS3 on ERK/AKT activity and reduced DIRAS3-mediated TFEB or FOXo3a nuclear localization and MAPLC3B expression in ovarian cancer cells. Treatment with antibodies against VEGF, IL-8, and IGF receptor inhibited the growth of dormant xenografts, thereby prolonging survival from 99 to >220 days (P < .05) and curing a percentage of mice.
conclusionsTreatment with a combination of anti-VEGF, anti-IL-8, and anti-IGF receptor antibodies prevented the outgrowth of dormant cells and prolonged survival in a preclinical model.
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