ArticleCancer research2016
Constitutive Activation of PI3K in Oocyte Induces Ovarian Granulosa Cell Tumors.
Article in Cancer research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.
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Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 46 citations in OpenAlex.
- Platelet-rich plasma and folliculogenesis: a systematic mechanistic review and computational pathway analysis.Frontiers in reproductive health · 2026Pooled it
- EPI-SauriCas9-based mouse ovarian cancer models recapitulating pten deletion in patients.Communications biology · 2025Article
- Pancreatic Damage in Ovarian Cancer-Associated Cachexia Is Driven by Activin A Signalling.Journal of cachexia, sarcopenia and muscle · 2025Article
- Leukemic Cells Infiltrate the Ovaries Without Damaging Ovarian Reserve in an Acute Myeloid Leukemia Mouse Model.Endocrinology · 2025Article
- Oocyte death is triggered by the stabilization of TAp63α dimers in response to cisplatin.Cell death & disease · 2024Article
- KIT in oocytes: a key factor for oocyte survival and reproductive lifespan.EBioMedicine · 2024Article
- Metabolic characteristics of granulosa cell tumor: role of PPARγ signaling†.Biology of reproduction · 2024Article
- TAp63 determines the fate of oocytes against DNA damage.Science advances · 2022Article
- Curcumin Alleviates Hyperandrogenism and Promotes Follicular Proliferation in Polycystic Ovary Syndrome Rats: Insights on IRS1/PI3K/GLUT4 and PTEN Modulations.Chinese journal of integrative medicine · 2022Article
- The Clinical Application of Growth Hormone and Its Biological and Molecular Mechanisms in Assisted Reproduction.International journal of molecular sciences · 2022Review
- Development of ovarian tumour causes significant loss of muscle and adipose tissue: a novel mouse model for cancer cachexia study.Journal of cachexia, sarcopenia and muscle · 2022Article
- Adult-type granulosa cell tumor of the ovary.American journal of cancer research · 2022Review
- Potential roles of experimental reproductive technologies in infertile women with diminished ovarian reserve.Journal of assisted reproduction and genetics · 2021Review
- Article
- Constitutive expression of progesterone receptor isoforms promotes the development of hormone-dependent ovarian neoplasms.Science signaling · 2020Article
- Continuous treatment with cisplatin induces the oocyte death of primordial follicles without activation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Ovarian granulosa cell tumor characterization identifies FOXL2 as an immunotherapeutic target.JCI insight · 2020Article
- Whole Genome Analysis of Ovarian Granulosa Cell Tumors Reveals Tumor Heterogeneity and a High-Grade TP53-Specific Subgroup.Cancers · 2020Article
- Review
- Development of syngeneic murine cell lines for use in immunocompetent orthotopic lung cancer models.Cancer cell international · 2020Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Cell-cell interactions play crucial roles in the maintenance of tissue homeostasis, a loss of which often leads to varying diseases, including cancer. Here, we report that uncontrolled PI3K activity within oocytes irreversibly transforms granulosa cells (GC), causing GC tumors (GCT) through perturbed local cell communication. Previously, we reported reproductive phenotypes of transgenic mice, in which expression of constitutively active mutant PI3K was induced in primordial oocytes by Gdf9-iCre. The transgenic mice (Cre(+)) demonstrated severe ovarian phenotypes, including the overgrowth of excess ovarian follicles and anovulation. Surprisingly, the Cre(+) mice became cachectic by postnatal day 80 due to bilateral GCT. Although GCT cells proliferated independently of oocytes, local interactions with mutant PI3K-positive oocytes during early folliculogenesis were essential for the GC transformation. Growing GCT cells expressed high levels of inhibin βA and nuclear SMAD3, and the proliferation rate was positively correlated with a high activin A to inhibin A ratio. These results suggested that the tumor cells stimulated their growth through an activin A autocrine signaling pathway, a hypothesis confirmed by activin A secretion in cultured GCT cells, which proliferated in response. Although communication between the oocyte and surrounding somatic cells is critical for the normal development of ovarian follicles, perturbations in oocyte-GC communication during early folliculogenesis can induce GCT by activating an autocrine growth circuit program in GC. Cancer Res; 76(13); 3851-61. ©2016 AACR.
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