ArticlePLoS computational biology2015
Causal Modeling of Cancer-Stromal Communication Identifies PAPPA as a Novel Stroma-Secreted Factor Activating NFκB Signaling in Hepatocellular Carcinoma.
Article in PLoS computational biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
What it found
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.
- Loss of alanine-glyoxylate and serine-pyruvate aminotransferase expression accelerated the progression of hepatocellular carcinoma and predicted poor prognosis.Journal of translational medicine · 2019Pooled it
- High Expression of PAPP-A Predicts Poor Outcomes in Oestrogen Receptor-Positive Breast Cancer Patients.Cancer medicine · 2026Article
- Pan-Cancer Analysis ofBiology · 2026Article
- Mitoepigenetics pathways and natural compounds: a dual approach to combatting hepatocellular carcinoma.Medical oncology (Northwood, London, England) · 2024Review
- The role of pregnancy associated plasma protein-A in triple negative breast cancer: a promising target for achieving clinical benefits.Journal of biomedical science · 2024Review
- Hepatic stellate cell-released CXCL1 aggravates HCC malignant behaviors through the MIR4435-2HG/miR-506-3p/TGFB1 axis.Cancer science · 2023Article
- Pregnancy-associated plasma protein A mRNA expression as a marker for differentiated thyroid cancer: results from a "surgical" and a "cytological" series.Journal of endocrinological investigation · 2022Article
- The portrait of liver cancer is shaped by mitochondrial genetics.Cell reports · 2022Article
- A systems pharmacology approach based on oncogenic signalling pathways to determine the mechanisms of action of natural products in breast cancer from transcriptome data.BMC complementary medicine and therapies · 2021Article
- Identification of Conserved Pappalysin 1-Derived Circular RNA-Mediated Competing Endogenous RNA in Osteosarcoma.Evolutionary bioinformatics online · 2021Article
- Recent Advances in Practical Methods for Liver Cell Biology: A Short Overview.International journal of molecular sciences · 2020Review
- Inhibition of mTORC2/RICTOR Impairs Melanoma Hepatic Metastasis.Neoplasia (New York, N.Y.) · 2018Article
- Recombinant PAPP-A resistant insulin-like growth factor binding protein 4 (dBP4) inhibits angiogenesis and metastasis in a murine model of breast cancer.BMC cancer · 2018Article
- Cellular network modeling and single cell gene expression analysis reveals novel hepatic stellate cell phenotypes controlling liver regeneration dynamics.BMC systems biology · 2018Article
- Pregnancy-associated plasma protein a in cancer: expression, oncogenic functions and regulation.American journal of cancer research · 2018Review
- Cabozantinib-induced osteoblast secretome promotes survival and migration of metastatic prostate cancer cells in bone.Oncotarget · 2017Article
- Gene expression profiling of tumor-initiating stem cells from mouse Krebs-2 carcinoma using a novel marker of poorly differentiated cells.Oncotarget · 2017Article
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Corrections and comments
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Inter-cellular communication with stromal cells is vital for cancer cells. Molecules involved in the communication are potential drug targets. To identify them systematically, we applied a systems level analysis that combined reverse network engineering with causal effect estimation. Using only observational transcriptome profiles we searched for paracrine factors sending messages from activated hepatic stellate cells (HSC) to hepatocellular carcinoma (HCC) cells. We condensed these messages to predict ten proteins that, acting in concert, cause the majority of the gene expression changes observed in HCC cells. Among the 10 paracrine factors were both known and unknown cancer promoting stromal factors, the former including Placental Growth Factor (PGF) and Periostin (POSTN), while Pregnancy-Associated Plasma Protein A (PAPPA) was among the latter. Further support for the predicted effect of PAPPA on HCC cells came from both in vitro studies that showed PAPPA to contribute to the activation of NFκB signaling, and clinical data, which linked higher expression levels of PAPPA to advanced stage HCC. In summary, this study demonstrates the potential of causal modeling in combination with a condensation step borrowed from gene set analysis [Model-based Gene Set Analysis (MGSA)] in the identification of stromal signaling molecules influencing the cancer phenotype.
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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.