ArticleOncogene2020
Targeting an autocrine IL-6-SPINK1 signaling axis to suppress metastatic spread in ovarian clear cell carcinoma.
Article in Oncogene, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
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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.
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Who cites it
23 citing papers in PubMed, 30 citations in OpenAlex.
- E-cadherin-driven interleukin-6 expression promotes autophagy-mediated platinum resistance in ovarian clear cell carcinoma.Cancer gene therapy · 2026Article
- SPINK1-driven cellular heterogeneity and interaction networks in intrahepatic cholangiocarcinoma revealed by integrated multi-omics analysis.Journal of advanced research · 2026Article
- PRSS23 promotes ovarian cancer peritoneal dissemination independent of protease activity.The Journal of biological chemistry · 2026Article
- Identification of an Anoikis-Related Gene Signature to Predict the Prognosis in Patients With Oral Squamous Cell Carcinoma.International dental journal · 2026Article
- Ovarian Cancer Stem Cells: Mechanisms of Progression and Therapeutic Strategies.Oncology research · 2026Review
- Anoikis resistance in Cancer: Mechanisms, therapeutic strategies, potential targets, and models for enhanced understanding.Cancer letters · 2025Review
- Inflammatory reprogramming of the solid tumor microenvironment by infiltrating clonal hematopoiesis is associated with adverse outcomes.Cell reports. Medicine · 2025Article
- SPINK1 facilitates tumor progression via the EGFR/JAK/STAT3 axis in oral squamous cell carcinoma: insights from single-cell RNA sequencing.Frontiers in oncology · 2025Article
- High SPINK1 Immunostaining in Colorectal Carcinoma is Associated with Poor Outcomes.Sultan Qaboos University medical journal · 2025Article
- The immunotherapy era in ovarian clear cell carcinoma: current evidence and future perspective.Frontiers in immunology · 2025Review
- Spatially resolved gene expression profiling of tumor microenvironment reveals key steps of lung adenocarcinoma development.Nature communications · 2024Article
- Prediction of response to promising first-line chemotherapy in ovarian cancer patients with residual peritoneal tumors: practical biomarkers and robust multiplex models.International journal of clinical oncology · 2024Article
- Targeting interleukin-6 as a treatment approach for peritoneal carcinomatosis.Journal of translational medicine · 2024Review
- Elucidating prognosis in cervical squamous cell carcinoma and endocervical adenocarcinoma: a novel anoikis-related gene signature model.Frontiers in oncology · 2024Article
- Machine learning and experiments identifies SPINK1 as a candidate diagnostic and prognostic biomarker for hepatocellular carcinoma.Discover oncology · 2023Article
- Article
- A novel oncolytic virus induces a regional cytokine storm and safely eliminates malignant ascites of colon cancer.Cancer medicine · 2022Article
- The senescence-associated secretory phenotype in ovarian cancer dissemination.American journal of physiology. Cell physiology · 2022Review
- SPINKs in Tumors: Potential Therapeutic Targets.Frontiers in oncology · 2022Review
- Epithelial Stem Cells: Making, Shaping and Breaking the Niche.Advances in experimental medicine and biology · 2022Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
A major clinical challenge of ovarian cancer is the development of malignant ascites accompanied by widespread peritoneal metastasis. In ovarian clear cell carcinoma (OCCC), a challenging subtype of ovarian cancer, this problem is compounded by near-universal primary chemoresistance; patients with advanced stage OCCC thus lack effective therapies and face extremely poor survival rates. Here we show that tumor-cell-expressed serine protease inhibitor Kazal type 1 (SPINK1) is a key driver of OCCC progression and metastasis. Using cell culture models of human OCCC, we find that shRNA silencing of SPINK1 sensitizes tumor cells to anoikis and inhibits proliferation. Knockdown of SPINK1 in OCCC cells also profoundly suppresses peritoneal metastasis in mouse implantation models of human OCCC. We next identify a novel autocrine signaling axis in OCCC cells whereby tumor-cell-produced interleukin-6 (IL-6) regulates SPINK1 expression to stimulate a common protumorigenic gene expression pattern leading to anoikis resistance and proliferation of OCCC cells. We further demonstrate that this signaling pathway can be successfully interrupted with the IL-6Rα inhibitor tocilizumab, sensitizing cells to anoikis in vitro and reducing metastasis in vivo. These results suggest that clinical trials of IL-6 pathway inhibitors in OCCC may be warranted, and that SPINK1 might offer a candidate predictive biomarker in this population.
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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.