ArticleOncogene2005
Lysophosphatidic acid and endothelin-induced proliferation of ovarian cancer cell lines is mitigated by neutralization of granulin-epithelin precursor (GEP), a prosurvival factor for ovarian cancer.
Article in Oncogene, 2005. 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, 69 citations in OpenAlex.
- Secretory leukocyte peptidase inhibitor as a dynamic radiotherapy response biomarker in esophageal squamous cell carcinoma.MedScience · 2026Article
- Repurposing colforsin daropate to treat MYC-driven high-grade serous ovarian carcinomas.Science signaling · 2024Article
- Progranulinopathy: A diverse realm of disorders linked to progranulin imbalances.Cytokine & growth factor reviews · 2024Review
- Review
- Progranulin promoted the proliferation, metastasis, and suppressed apoptosis via JAK2-STAT3/4 signaling pathway in papillary thyroid carcinoma.Cancer cell international · 2023Article
- A narrative review of multiple mechanisms of progranulin in cancer: a potential target for anti-cancer therapy.Translational cancer research · 2021Review
- Prognostic significance of serum progranulin level in de novo adult acute lymphoblastic leukemia patients.Clinical and experimental medicine · 2020Article
- Inhibition of PI3K/AKT/mTOR and MAPK signaling pathways decreases progranulin expression in ovarian clear cell carcinoma (OCCC) cell line: a potential biomarker for therapy response to signaling pathway inhibitors.Medical oncology (Northwood, London, England) · 2019Article
- Insights into exchange factor directly activated by cAMP (EPAC) as potential target for cancer treatment.Molecular and cellular biochemistry · 2018Review
- Progranulin and its biological effects in cancer.Medical oncology (Northwood, London, England) · 2017Review
- Foxo4- and Stat3-dependent IL-10 production by progranulin in regulatory T cells restrains inflammatory arthritis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2017Article
- Acetoacetate Accelerates Muscle Regeneration and Ameliorates Muscular Dystrophy in Mice.The Journal of biological chemistry · 2016Article
- Copy number gain of granulin-epithelin precursor (GEP) at chromosome 17q21 associates with overexpression in human liver cancer.BMC cancer · 2015Article
- Progranulin promotes colorectal cancer proliferation and angiogenesis through TNFR2/Akt and ERK signaling pathways.American journal of cancer research · 2015Article
- Targeted manipulation of the sortilin-progranulin axis rescues progranulin haploinsufficiency.Human molecular genetics · 2014Article
- Hax-1 is required for Rac1-Cortactin interaction and ovarian carcinoma cell migration.Genes & cancer · 2014Article
- The anti-adipogenic effect of PGRN on porcine preadipocytes involves ERK1,2 mediated PPARγ phosphorylation.Molecular biology reports · 2013Article
- Tumor immunology: multidisciplinary science driving basic and clinical advances.Cancer immunology research · 2013Article
- Insights into the role of progranulin in immunity, infection, and inflammation.Journal of leukocyte biology · 2013Review
- Mechanisms of granulin deficiency: lessons from cellular and animal models.Molecular neurobiology · 2013Review
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 1 country.
Funding
Abstract
Granulin-epithelin precursor (GEP/progranulin) is an autocrine growth factor for ovarian cancer. We examined the production and function of GEP and report that: (1) GEP production is regulated by endothelin (ET-1), lysophosphatidic acid (LPA), and cAMP; (2) cAMP signals GEP production through exchange protein activated by cAMP (EPAC); (3) ET-1 and cAMP/EPAC induce GEP through ERK1/2; and (4) neutralization of GEP results in apoptosis. Exposure of HEY-A8 and OVCAR3 ovarian cancer cells to LPA and ET-1 yielded GEP production and secretion in a dose- and time-dependent fashion; neither stimulated significant concentrations of cAMP directly. Stimulation of cAMP production with pertussis and cholera toxin, or forskolin induced GEP in a PKA-independent fashion. EPAC, an intracellular cAMP receptor, is activated specifically by the cAMP analog, 8-CPT-2'-O-Me-cAMP (8-CPT); 8-CPT treatment stimulated GEP production and secretion. The MEK inhibitor, U0126, abrogated GEP production in response to ET-1 and 8-CPT, confirming involvement of MAPK. A partial inhibition of basal and stimulated GEP production was observed when cells were treated with a internal calcium chelator, BAPTA. Neutralizing anti-GEP antibody reversed basal as well as LPA, ET-1 and 8-CPT-induced ovarian cancer cell growth and induced apoptosis as demonstrated by caspase-3 and PARP cleavage, DNA fragmentation, and nuclear condensation. These results indicate that GEP is a growth and survival factor for ovarian cancer, induced by LPA and ET-1 and cAMP/EPAC through ERK1/2.
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Registered trials
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