ArticleGenes & cancer2011
Lysophosphatidic Acid Stimulates the Proliferation of Ovarian Cancer Cells via the gep Proto-Oncogene Gα(12).
Article in Genes & cancer, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 42 citations in OpenAlex.
- Gintonin prevents paclitaxel-induced neuropathic pain via spinal LPAJournal of ginseng research · 2026Article
- Impact of tumor necrosis factor-alpha and lysophosphatidic acid on the behavior of ovarian cancer cells in a three-dimensional collagen hydrogel.The journal of obstetrics and gynaecology research · 2025Article
- Article
- Lysophosphatidic Acid Receptor 3 (LPA3): Signaling and Phosphorylation Sites.International journal of molecular sciences · 2024Article
- Deciphering a GPCR-lncrna-miRNA nexus: Identification of an aberrant therapeutic target in ovarian cancer.Cancer letters · 2024Article
- LPAInternational journal of molecular sciences · 2024Article
- Synthesis and Biological Evaluation of Lysophosphatidic Acid Analogues Using Conformational Restriction and Bioisosteric Replacement Strategies.ACS omega · 2023Article
- Review
- Identification ofOncology letters · 2021Article
- The LPAInternational journal of molecular sciences · 2021Review
- Differential effects of thymoquinone on lysophosphatidic acid-induced oncogenic pathways in ovarian cancer cells.Journal of traditional and complementary medicine · 2020Article
- Tumor necrosis factor receptor modulator spermatogenesis-associated protein 2 is a novel predictor of outcome in ovarian cancer.Cancer science · 2019Article
- Emerging Roles of Primary Cilia in Glioma.Frontiers in cellular neuroscience · 2019Review
- Ascites IL-10 Promotes Ovarian Cancer Cell Migration.Cancer microenvironment : official journal of the International Cancer Microenvironment Society · 2018Article
- Activity and clinical relevance of autotaxin and lysophosphatidic acid pathways in high-grade serous carcinoma.Virchows Archiv : an international journal of pathology · 2018Article
- Article
- LPA signaling is regulated through the primary cilium: a novel target in glioblastoma.Oncogene · 2018Article
- Aberrant expression of JNK-associated leucine-zipper protein, JLP, promotes accelerated growth of ovarian cancer.Oncotarget · 2016Article
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- Article
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
Lysophosphatidic acid (LPA), an agonist that activates specific G protein-coupled receptors, is present at an elevated concentration in the serum and ascitic fluid of ovarian cancer patients. Although the increased levels of LPA have been linked to the genesis and progression of different cancers including ovarian carcinomas, the specific signaling conduit utilized by LPA in promoting different aspects of oncogenic growth has not been identified. Here, we show that LPA stimulates both migration and proliferation of ovarian cancer cells. Using multiple approaches, we demonstrate that the stimulation of ovarian cancer cells with LPA results in a robust and statistically significant proliferative response. Our results also indicate that Gα(12), the gep proto-oncogene, which can be stimulated by LPA via specific LPA receptors, is overtly activated in a large array of ovarian cancer cells. We further establish that LPA stimulates the rapid activation of Gα(12) in SKOV-3 cells and the expression of CT12, an inhibitory minigene of Gα(12) that disrupts LPAR-Gα(12) interaction and potently inhibits such activation. Using this inhibitory molecule as well as the shRNA approach, we show that the inhibition of Gα(12) or silencing of its expression drastically and significantly attenuates LPA-mediated proliferation of ovarian cancer cell lines such as SKOV3, Hey, and OVCAR-3. Together with our findings that the silencing of Gα(12) does not have any significant effect on LPA-mediated migratory response of SKOV3 cells, our results point to a critical role for LPA-LPAR-Gα(12) signaling in ovarian cancer cell proliferation and not in migration. Thus, results presented here for the first time demonstrate that the gep proto-oncogene forms a specific node in LPA-LPAR-mediated mitogenic signaling in ovarian cancer cells.
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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.