ArticleeLife2015
FAK/PYK2 promotes the Wnt/β-catenin pathway and intestinal tumorigenesis by phosphorylating GSK3β.
Article in eLife, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers, 1 of them a synthesis that pooled it.
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Who cites it
81 citing papers in PubMed, 1 synthesis or guideline pooled it, 119 citations in OpenAlex.
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- CPZ promotes the proliferation of gastric cancer by activating the Wnt pathway through binding with DVL2.Discover oncology · 2025Article
- Antiosteoporotic activity of nodakenetin, a coumarin compound fromJournal of traditional and complementary medicine · 2025Article
- Focal Adhesion Kinase Intersects With the BRD4-MYC Axis and YAP1 to Drive Tumor Cell Growth, Phenotypic Plasticity, Stemness, and Metastatic Potential in Colorectal Cancer.Cancer medicine · 2025Article
- Targeting the hydrophobic pockets of FAK/PYK2 FAT domain: a highly effective inhibitory strategy suppressing tumor growth and eliminating metastasis.Cell communication and signaling : CCS · 2025Article
- Fatty acid uptake activates an AXL-CAV1-β-catenin axis to drive melanoma progression.Genes & development · 2025Article
- SYT4 Interacts with PSMC6 to Facilitate Malignant Progression in Gastric Carcinoma via Activating Wnt/β-catenin Signaling.International journal of biological sciences · 2025Article
- Research progress of PYK2 in digestive system diseases.Frontiers in immunology · 2025Review
- Selective Pyk2 inhibition enhances bone restoration through SCARA5-mediated bone marrow remodeling in ovariectomized mice.Cell communication and signaling : CCS · 2024Article
- Gene inactivation of lysyl oxidase in smooth muscle cells reduces atherosclerosis burden and plaque calcification in hyperlipidemic mice.Atherosclerosis · 2024Article
- Focal adhesion kinase signaling - tumor vulnerabilities and clinical opportunities.Journal of cell science · 2024Review
- Acinar to β-like cell conversion through inhibition of focal adhesion kinase.Nature communications · 2024Article
- ALK upregulates POSTN and WNT signaling to drive neuroblastoma.Cell reports · 2024Article
- WSB1, as an E3 ligase, restrains myocardial ischemia-reperfusion injury by activating β-catenin signaling via promoting GSK3β ubiquitination.Molecular medicine (Cambridge, Mass.) · 2024Article
- The Effect of Adipocyte-Secreted Factors in Activating Focal Adhesion Kinase-Mediated Cell Signaling Pathway towards Metastasis in Breast Cancer Cells.International journal of molecular sciences · 2023Article
- Nonsense mutation suppression is enhanced by targeting different stages of the protein synthesis process.PLoS biology · 2023Article
21 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Aberrant activation of Wnt/β-catenin signaling plays an unequivocal role in colorectal cancer, but identification of effective Wnt inhibitors for use in cancer remains a tremendous challenge. New insights into the regulation of this pathway could reveal new therapeutic point of intervention, therefore are greatly needed. Here we report a novel FAK/PYK2/GSK3β(Y216)/β-catenin regulation axis: FAK and PYK2, elevated in adenomas in APC(min/+) mice and in human colorectal cancer tissues, functioned redundantly to promote the Wnt/β-catenin pathway by phosphorylating GSK3β(Y216) to reinforce pathway output-β-catenin accumulation and intestinal tumorigenesis. We previously showed that Wnt-induced β-catenin accumulation requires Wnt-induced GSK3β/β-TrCP interaction; the current study revealed that phosphorylation of GSK3β(Y216) was a molecular determinant of GSK3β recruitment of β-TrCP. Pharmacological inhibition of FAK/PYK2 suppressed adenoma formation in APC(min/+) mice accompanied with reduced intestinal levels of phospho-GSK3β(Y216) and β-catenin, indicating that FAK/PYK2/GSK3β(Y216) axis is critical for the activation of Wnt/β-catenin signaling in APC driven intestinal tumorigenesis.
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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.