ArticleProceedings of the National Academy of Sciences of the United States of America2015
Netrin-1 exerts oncogenic activities through enhancing Yes-associated protein stability.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 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
24 citing papers in PubMed, 39 citations in OpenAlex.
- Endothelial UNC5B regulates blood‑retinal barrier homeostasis.International journal of molecular medicine · 2026Article
- Epstein-Barr virus infection upregulates extracellular OLFM4 to activate YAP signaling during gastric cancer progression.Nature communications · 2024Article
- Research progress of the netrins and their receptors in cancer.Journal of cellular and molecular medicine · 2024Review
- MicroRNA PC-3p-2869 Regulates Antler Growth and Inhibits Proliferation and Migration of Human Osteosarcoma and Chondrosarcoma Cells by Targeting CDK8, EEF1A1, and NTN1.International journal of molecular sciences · 2023Article
- Increased Expression Levels of Netrin-1 in Visceral Adipose Tissue during Obesity Favour Colon Cancer Cell Migration.Cancers · 2023Article
- An Overview of the Molecular Cues and Their Intracellular Signaling Shared by Cancer and the Nervous System: From Neurotransmitters to Synaptic Proteins, Anatomy of an All-Inclusive Cooperation.International journal of molecular sciences · 2022Review
- Article
- Article
- Targeting the ILK/YAP axis by LFG-500 blocks epithelial-mesenchymal transition and metastasis.Acta pharmacologica Sinica · 2021Article
- The intracellular domain of UNC5B facilities proliferation and metastasis of bladder cancer cells.Journal of cellular and molecular medicine · 2021Article
- Netrin1 deficiency activates MST1 via UNC5B receptor, promoting dopaminergic apoptosis in Parkinson's disease.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Yes-associated protein (YAP) and transcriptional coactivator with a PDZ-binding motif (TAZ): a nexus between hypoxia and cancer.Acta pharmaceutica Sinica. B · 2020Review
- A network map of netrin receptor UNC5B-mediated signaling.Journal of cell communication and signaling · 2019Article
- LKB1 and YAP phosphorylation play important roles in Celastrol-induced β-catenin degradation in colorectal cancer.Therapeutic advances in medical oncology · 2019Article
- Making Connections: Guidance Cues and Receptors at Nonneural Cell-Cell Junctions.Cold Spring Harbor perspectives in biology · 2018Review
- Netrin-1 promotes glioma growth by activating NF-κB via UNC5A.Scientific reports · 2017Article
- An FAK-YAP-mTOR Signaling Axis Regulates Stem Cell-Based Tissue Renewal in Mice.Cell stem cell · 2017Article
- Integrated analysis identifies microRNA-195 as a suppressor of Hippo-YAP pathway in colorectal cancer.Journal of hematology & oncology · 2017Article
- Multiparametric Analysis of Cell Shape Demonstrates that β-PIX Directly Couples YAP Activation to Extracellular Matrix Adhesion.Cell systems · 2017Article
- Jasplakinolide induces primary cilium formation through cell rounding and YAP inactivation.PloS one · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 4 institutions in 1 country.
Funding
Abstract
Yes-associated protein (YAP), a transcription coactivator, is the major downstream effector of the Hippo pathway, which plays a critical role in organ size control and cancer development. However, how YAP is regulated by extracellular stimuli in tumorigenesis remains incompletely understood. Netrin-1, a laminin-related secreted protein, displays proto-oncogenic activity in cancers. Nonetheless, the downstream signaling mediating its oncogenic effects is not well defined. Here we show that netrin-1 via its transmembrane receptors, deleted in colorectal cancer and uncoordinated-5 homolog, up-regulates YAP expression, escalating YAP levels in the nucleus and promoting cancer cell proliferation and migration. Inactivating netrin-1, deleted in colorectal cancer, or uncoordinated-5 homolog B (UNC5B) decreases YAP protein levels, abrogating cancer cell progression by netrin-1, whereas knockdown of mammalian STE20-like protein kinase 1/2 (MST1/2) or large tumor suppressor kinase 1/2 (Lats1/2), two sets of upstream core kinases of the Hippo pathway, has no effect in blocking netrin-1-induced up-regulation of YAP. Netrin-1 stimulates phosphatase 1A to dephosphorylate YAP, which leads to decreased ubiquitination and degradation, enhancing YAP accumulation and signaling. Hence, our findings support that netrin-1 exerts oncogenic activity through YAP signaling, providing a mechanism coupling extracellular signals to the nuclear YAP oncogene.
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.