ArticleThe Journal of clinical investigation2021
Inhibition of relaxin autocrine signaling confers therapeutic vulnerability in ovarian cancer.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06808165 (Evaluation of Relaxin and Placental Volume in Placenta Accreta Spectrum Disorders), which is not on this map. Cited by 20 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Evaluation of Relaxin and Placental Volume in Placenta Accreta Spectrum Disorders: A Case-Control Study
Who cites it
20 citing papers in PubMed, 30 citations in OpenAlex.
- Article
- Metabolically engineered probiotic OMVs as nanovaccine mediating sequential immunomodulation for chronic bone infection immunotherapy.Cell reports. Medicine · 2026Article
- Divergent activation of the RXFP1 relaxin receptor by protein and small molecule agonists.bioRxiv : the preprint server for biology · 2026Article
- Molecular Characteristics, Potential Mechanisms, and Prognostic Gene Model of Younger Female Patients With Gastric Cancer.Cancer reports (Hoboken, N.J.) · 2026Article
- Mendelian Randomization and ScTranscriptomics Reveal a Lipid Low Malignant Cells Driving Immunosuppression and Matrix Remodeling in Oral squamous cell carcinoma.International dental journal · 2026Article
- Machine learning enables efficient and effective affinity maturation of nanobodies.bioRxiv : the preprint server for biology · 2026Article
- Single-cell RNA sequencing reveals genes relevant to periodontal therapy and periodontitis.Physiological genomics · 2025Article
- Systems biology-driven identification of biomarkers and significant pathways in radiation-induced hormone-sensitive cancers.Discover oncology · 2025Article
- 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
- Role of Relaxin Signaling in Cancer: A Review.Biochemical pharmacology · 2024Review
- Relaxin-2 is a novel biomarker for differentiated thyroid carcinoma in humans.Biochemical pharmacology · 2024Article
- The diverse influences of relaxin-like peptide family on tumor progression: Potential opportunities and emerging challenges.Heliyon · 2024Review
- The dual and multifaceted role of relaxin-2 in cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2023Review
- Development of Novel High-Affinity Antagonists for the Relaxin Family Peptide Receptor 1.ACS pharmacology & translational science · 2023Article
- Histone methyltransferase SETD1A interacts with notch and promotes notch transactivation to augment ovarian cancer development.BMC cancer · 2023Article
- The Cell Surface Heparan Sulfate Proteoglycan Syndecan-3 Promotes Ovarian Cancer Pathogenesis.International journal of molecular sciences · 2022Article
- Review
- Evaluation of pharmacological activities and active components inFrontiers in nutrition · 2022Article
- Differential Expression of the Androgen Receptor, Splice Variants and Relaxin 2 in Renal Cancer.Life (Basel, Switzerland) · 2021Article
Corrections and comments
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Authors and funding
13 authors at 6 institutions in 2 countries.
Funding
Abstract
Ovarian cancer (OC) is the most deadly gynecological malignancy, with unmet clinical need for new therapeutic approaches. The relaxin peptide is a pleiotropic hormone with reproductive functions in the ovary. Relaxin induces cell growth in several types of cancer, but the role of relaxin in OC is poorly understood. Here, using cell lines and xenograft models, we demonstrate that relaxin and its associated GPCR RXFP1 form an autocrine signaling loop essential for OC in vivo tumorigenesis, cell proliferation, and viability. We determined that relaxin signaling activates expression of prooncogenic pathways, including RHO, MAPK, Wnt, and Notch. We found that relaxin is detectable in patient-derived OC tumors, ascites, and serum. Further, inflammatory cytokines IL-6 and TNF-α activated transcription of relaxin via recruitment of STAT3 and NF-κB to the proximal promoter, initiating an autocrine feedback loop that potentiated expression. Inhibition of RXFP1 or relaxin increased cisplatin sensitivity of OC cell lines and abrogated in vivo tumor formation. Finally, we demonstrate that a relaxin-neutralizing antibody reduced OC cell viability and sensitized cells to cisplatin. Collectively, these data identify the relaxin/RXFP1 autocrine loop as a therapeutic vulnerability in OC.
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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.