ArticleOncogene2020
A gain-of-functional screen identifies the Hippo pathway as a central mediator of receptor tyrosine kinases during tumorigenesis.
Article in Oncogene, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 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
53 citing papers in PubMed, 74 citations in OpenAlex.
- EphA2 as an oncogenic driver: roles and mechanisms of action in cancer.Molecular biology reports · 2026Review
- Bemarituzumab Suppresses Choroidal Neovascularization in Mice by Downregulating Melanoma Cell Adhesion Molecule and Yes-Associated Protein 1.ACS pharmacology & translational science · 2026Article
- Targeting TYRO3 attenuates apoptotic cell-driven cancer stemness in triple negative breast cancer.Cell communication and signaling : CCS · 2026Article
- [Mechanisms of Macrophage Efferocytosis-driven Remodeling of Lung Cancer Microenvironment Structure and Angiogenesis and Prospects for Clinical Intervention].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2026Review
- FGFR1/YAP1 signaling in endothelial cells drives renal fibrosis and offers a therapeutic target.Frontiers in pharmacology · 2026Article
- Gain-of-Functional Genomic Screening for Microproteins Essential for Tumorigenesis.Methods in molecular biology (Clifton, N.J.) · 2026Article
- FGF2-regulated Osteogenic Differentiation of Human Bone Marrow Stromal Cells.Current stem cell research & therapy · 2026Article
- Alexidine is a TAZ-specific small-molecule inhibitor that suppresses breast cancer invasion and metastasis.iScience · 2025Article
- Integrative High-Throughput RNAi Screening Identifies BRSK1, STK32C and STK40 as Novel Activators of YAP/TAZ.International journal of molecular sciences · 2025Article
- Posttranslational modifications of YAP/TAZ: molecular mechanisms and therapeutic opportunities.Cellular & molecular biology letters · 2025Review
- Application of Fluorescence- and Bioluminescence-Based Biosensors in Cancer Drug Discovery.Biosensors · 2024Review
- Article
- EphA2 promotes the transcription of KLF4 to facilitate stemness in oral squamous cell carcinoma.Cellular and molecular life sciences : CMLS · 2024Article
- Identification of PTPN12 Phosphatase as a Novel Negative Regulator of Hippo Pathway Effectors YAP/TAZ in Breast Cancer.International journal of molecular sciences · 2024Article
- Development of Novel Bioluminescent Biosensors Monitoring the Conformation and Activity of the Merlin Tumour Suppressor.International journal of molecular sciences · 2024Article
- Article
- Tasmanian devil cathelicidins exhibit anticancer activity against Devil Facial Tumour Disease (DFTD) cells.Scientific reports · 2023Article
- Extracellular vesicles in fatty liver promote a metastatic tumor microenvironment.Cell metabolism · 2023Article
- TYRO3 blockade enhances anti-PD-1 therapy response by modulating expression of CCN1 in tumor microenvironment.Journal for immunotherapy of cancer · 2023Article
- Loss-of-function mutations of SOX17 lead to YAP/TEAD activation-dependent malignant transformation in endometrial cancer.Oncogene · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
The Hippo pathway has emerged as a key signaling pathway that regulates various biological functions. Dysregulation of the Hippo pathway has been implicated in a broad range of human cancer types. While a number of stimuli affecting the Hippo pathway have been reported, its upstream kinase and extracellular regulators remain largely unknown. Here we performed the first comprehensive gain-of-functional screen for receptor tyrosine kinases (RTKs) regulating the Hippo pathway using an RTK overexpression library and a Hippo signaling activity biosensor. Surprisingly, we found that the majority of RTKs could regulate the Hippo signaling activity. We further characterized several of these novel relationships [TAM family members (TYRO3, AXL, METRK), RET, and FGFR family members (FGFR1 and FGFR2)] and found that the Hippo effectors YAP/TAZ are central mediators of the tumorigenic phenotypes (e.g., increased cell proliferation, transformation, increased cell motility, and angiogenesis) induced by these RTKs and their extracellular ligands (Gas6, GDNF, and FGF) through either PI3K or MAPK signaling pathway. Significantly, we identify FGFR, RET, and MERTK as the first RTKs that can directly interact with and phosphorylate YAP/TAZ at multiple tyrosine residues independent of upstream Hippo signaling, thereby activating their functions in tumorigenesis. In conclusion, we have identified several novel kinases and extracellular stimuli regulating the Hippo pathway. Our findings also highlight the pivotal role of the Hippo pathway in mediating Gas6/GDNF/FGF-TAM/RET/FGFR-MAPK/PI3K signaling during tumorigenesis and provide a compelling rationale for targeting YAP/TAZ in RTK-driven cancers.
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.