ArticleThe Journal of biological chemistry2016
Hypoxia and Transforming Growth Factor β Cooperate to Induce Fibulin-5 Expression in Pancreatic Cancer.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
32 citing papers in PubMed, 46 citations in OpenAlex.
- Fibulin-5 (FBLN5) as a context-dependent pan-cancer regulator: integrated multi-omics analysis reveals dual roles in tumor progression and therapeutic resistance.Translational cancer research · 2026Article
- Review
- Cancer-associated fibroblasts enhance colorectal cancer lymphatic metastasis via CLEC11A/LGR5-mediated WNT pathway activation.The Journal of clinical investigation · 2025Article
- Cluster Headache and Hypoxia: Breathing New Life into an Old Theory, with Novel Implications.Neurology international · 2024Review
- Anatomical and immunohistochemical analyses of the fusion of the premaxillary-maxillary suture in human fetuses.Journal of orofacial orthopedics = Fortschritte der Kieferorthopadie : Organ/official journal Deutsche Gesellschaft fur Kieferorthopadie · 2024Article
- FBLN5 as One Presumably Prognostic Gene Potentially Modulating Tumor Immune Microenvironment for Renal Clear Cell Carcinoma in Children and Young Adults.Pharmacogenomics and personalized medicine · 2024Article
- Loss of NDUFS1 promotes gastric cancer progression by activating the mitochondrial ROS-HIF1α-FBLN5 signaling pathway.British journal of cancer · 2023Article
- Article
- Tumor microenvironment interactions with cancer stem cells in pancreatic ductal adenocarcinoma.Advances in cancer research · 2023Review
- Review
- Review
- Elastic Fibre Proteins in Elastogenesis and Wound Healing.International journal of molecular sciences · 2022Review
- Recent Developments in the Study of the Microenvironment of Cancer and Drug Delivery.Current drug metabolism · 2022Article
- Role of reactive oxygen species in tumors based on the 'seed and soil' theory: A complex interaction (Review).Oncology reports · 2021Review
- Article
- Modulation of cell physiology under hypoxia in pancreatic cancer.World journal of gastroenterology · 2021Review
- Role of Fibulins in Embryonic Stage Development and Their Involvement in Various Diseases.Biomolecules · 2021Review
- Interplay between tumor microenvironment and partial EMT as the driver of tumor progression.iScience · 2021Review
- Targeting hypoxic tumor microenvironment in pancreatic cancer.Journal of hematology & oncology · 2021Review
- Endothelial TGF-β signaling instructs smooth muscle cell development in the cardiac outflow tract.eLife · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
The deposition of extracellular matrix (ECM) is a defining feature of pancreatic ductal adenocarcinoma (PDA), where ECM signaling can promote cancer cell survival and epithelial plasticity programs. However, ECM signaling can also limit PDA tumor growth by producing cytotoxic levels of reactive oxygen species. For example, excess fibronectin stimulation of α5β1 integrin on stromal cells in PDA results in reduced angiogenesis and increased tumor cell apoptosis because of oxidative stress. Fibulin-5 (Fbln5) is a matricellular protein that blocks fibronectin-integrin interaction and thus directly limits ECM-driven reactive oxygen species production and supports PDA progression. Compared with normal pancreatic tissue, Fbln5 is expressed abundantly in the stroma of PDA; however, the mechanisms underlying the stimulation of Fbln5 expression in PDA are undefined. Using in vitro and in vivo approaches, we report that hypoxia triggers Fbln5 expression in a TGF-β- and PI3K-dependent manner. Pharmacologic inhibition of TGF-β receptor, PI3K, or protein kinase B (AKT) was found to block hypoxia-induced Fbln5 expression in mouse embryonic fibroblasts and 3T3 fibroblasts. Moreover, tumor-associated fibroblasts from mouse PDA were also responsive to TGF-β receptor and PI3K/AKT inhibition with regard to suppression of Fbln5. In genetically engineered mouse models of PDA, therapy-induced hypoxia elevated Fbln5 expression, whereas pharmacologic inhibition of TGF-β signaling reduced Fbln5 expression. These findings offer insight into the signaling axis that induces Fbln5 expression in PDA and a potential strategy to block its production.
Indexed as
Identifiers
What OpenQuestion holds
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.