ArticleCell stem cell2020
Lats1/2 Sustain Intestinal Stem Cells and Wnt Activation through TEAD-Dependent and Independent Transcription.
Article in Cell stem cell, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 99 papers.
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Who cites it
99 citing papers in PubMed, 201 citations in OpenAlex.
- Stemness in Colon Cancer.Methods in molecular biology (Clifton, N.J.) · 2027Article
- ADORA1 inhibition suppresses colon cancer development via hippo tumor suppressor pathway.Cell death and differentiation · 2026Article
- Genetic Medicine Approaches for Tumor Suppressor Loss: Therapeutic Replacement with Self-Amplifying RNA.Pharmaceutical research · 2026Review
- Current Status of Intestinal Stem Cell Research: Mechanisms, Intestinal Diseases, and Organoid Development.Cells · 2026Review
- Targeting cancer signaling pathways and their therapeutic strategies.Discover oncology · 2026Review
- Targeting YAP-TEAD Interaction with Honokiol to Inhibit Melanoma Progression and Metastasis.Biomolecules & therapeutics · 2026Article
- Bridging metabolic reprogramming and targeted therapy: the critical role of S-palmitoylation in cancer.Frontiers in cell and developmental biology · 2026Review
- In vitro evaluation of Verteporfin and exploration of TEAD palmitoylation inhibition in Piezo1-YAP/TAZ signaling and ECM remodeling.Scientific reports · 2025Article
- FAM189A2 activates Hippo signaling pathway by abrogating WWP2-mediated LATS1 ubiquitination, to inhibit the glycolysis and proliferation processes of lung adenocarcinoma.Journal of translational medicine · 2025Article
- Lats1/2 Differentially Modulate the Proliferative State of Dental Epithelial Progenitors and Ameloblasts in the Murine Incisor.Orthodontics & craniofacial research · 2025Article
- Microbial membrane vesicles and the intestinal epithelium: a crosstalk in health and disease.Archives of microbiology · 2025Review
- Targeting the Hippo pathway in cancer.Nature reviews. Drug discovery · 2025Review
- NCAPH-YAP1 interaction promotes breast cancer stemness and tumor progression.Stem cell research & therapy · 2025Article
- Article
- Epithelial-Mesenchymal Transition Activates YAP to Drive Malignant Progression and Immune Evasion.Cancers · 2025Article
- YAP regulates transcriptional programs for layer-specific periosteal expansion during fracture repair.Science advances · 2025Article
- TEAD-targeting small molecules induce a cofactor switch to regulate the Hippo pathway.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Article
- The Hippo pathway effector YAP inhibits NF-κB signaling and ccRCC growth by opposing ZHX2.The Journal of biological chemistry · 2025Article
- Targeting the disrupted Hippo signaling to prevent neoplastic renal epithelial cell immune evasion.Nature communications · 2025Article
39 more citing papers are in PubMed but not listed here.
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Authors and funding
20 authors at 7 institutions in 1 country.
Funding
Abstract
Intestinal homeostasis is tightly regulated by complex yet poorly understood signaling networks. Here, we demonstrate that Lats1/2, the core Hippo kinases, are essential to maintain Wnt pathway activity and intestinal stem cells. Lats1/2 deletion leads to loss of intestinal stem cells but drives Wnt-uncoupled crypt expansion. To explore the function of downstream transcriptional enhanced associate domain (TEAD) transcription factors, we identified a selective small-molecule reversible inhibitor of TEAD auto-palmitoylation that directly occupies its lipid-binding site and inhibits TEAD-mediated transcription in vivo. Combining this chemical tool with genetic and proteomics approaches, we show that intestinal Wnt inhibition by Lats deletion is Yes-associated protein (YAP)/transcriptional activator with PDZ-binding domain (TAZ) dependent but TEAD independent. Mechanistically, nuclear YAP/TAZ interact with Groucho/Transducin-Like Enhancer of Split (TLE) to block Wnt/T-cell factor (TCF)-mediated transcription, and dual inhibition of TEAD and Lats suppresses Wnt-uncoupled Myc upregulation and epithelial over-proliferation in Adenomatous polyposis coli (APC)-mutated intestine. Our studies highlight a pharmacological approach to inhibit TEAD palmitoylation and have important implications for targeting Wnt and Hippo signaling in human malignancies.
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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.