ArticleThe Journal of biological chemistry2010
The Wnt/planar cell polarity protein-tyrosine kinase-7 (PTK7) is a highly efficient proteolytic target of membrane type-1 matrix metalloproteinase: implications in cancer and embryogenesis.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers, 1 of them a synthesis that pooled it.
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Who cites it
61 citing papers in PubMed, 1 synthesis or guideline pooled it, 93 citations in OpenAlex.
- Genetics of breast cancer bone metastasis: a sequential multistep pattern.Clinical & experimental metastasis · 2014Pooled it
- A guide to the types, structures, and multifaceted functions of matrix metalloproteinases in cancer.The FEBS journal · 2026Review
- Decoding the genetic architecture of hernia through genome-wide association and multi-trait analyses.medRxiv : the preprint server for health sciences · 2026Article
- Spatiotemporal Organization of PTK7 Diffusion on Cell Surface Facilitates Tumor Invasion and Migration.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Planar cell polarity zebrafish models of congenital scoliosis reveal underlying defects in notochord morphogenesis.Development (Cambridge, England) · 2024Article
- Impending role of inflammatory markers and their specificity and sensitivity in breast cancer patients.Scientific reports · 2024Article
- Recent insights into the therapeutic strategies targeting the pseudokinase PTK7 in cancer.Oncogene · 2024Review
- Article
- PTK7: an underestimated contributor to human cancer.Frontiers in oncology · 2024Review
- Disease modeling of ADAMTS9-related nephropathy using kidney organoids reveals its roles in tubular cells and podocytes.Frontiers in medicine · 2023Article
- Matrix Metalloproteinases in Chemoresistance: Regulatory Roles, Molecular Interactions, and Potential Inhibitors.Journal of oncology · 2022Review
- Matrix Metalloproteinases Shape the Tumor Microenvironment in Cancer Progression.International journal of molecular sciences · 2021Review
- Non-canonical Wnt signaling promotes directed migration of intestinal stem cells to sites of injury.Nature communications · 2021Article
- Targeting Wnt Signaling in Endometrial Cancer.Cancers · 2021Review
- Protein Tyrosine Kinase 7 Regulates EGFR/Akt Signaling Pathway and Correlates With Malignant Progression in Triple-Negative Breast Cancer.Frontiers in oncology · 2021Article
- An Overview of Potential Therapeutic Agents Targeting WNT/PCP Signaling.Handbook of experimental pharmacology · 2021Review
- Targeting Extracellular Matrix Remodeling Restores BRAF Inhibitor Sensitivity in BRAFi-resistant Melanoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2020Article
- The Wnt Signalling Pathway: A Tailored Target in Cancer.International journal of molecular sciences · 2020Review
- Spatio-temporal and Cellular Expression Patterns of PTK7 in the Healthy and Traumatically Injured Rat and Human Spinal Cord.Cellular and molecular neurobiology · 2020Article
- MT1-MMP deficiency leads to defective ependymal cell maturation, impaired ciliogenesis, and hydrocephalus.JCI insight · 2020Article
1 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
PTK7 is an essential component of the Wnt/planar cell polarity (PCP) pathway. We provide evidence that the Wnt/PCP pathway converges with pericellular proteolysis in both normal development and cancer. Here, we demonstrate that membrane type-1 matrix metalloproteinase (MT1-MMP), a key proinvasive proteinase, functions as a principal sheddase of PTK7. MT1-MMP directly cleaves the exposed PKP(621)↓LI sequence of the seventh Ig-like domain of the full-length membrane PTK7 and generates, as a result, an N-terminal, soluble PTK7 fragment (sPTK7). The enforced expression of membrane PTK7 in cancer cells leads to the actin cytoskeleton reorganization and the inhibition of cell invasion. MT1-MMP silencing and the analysis of the uncleavable L622D PTK7 mutant confirm the significance of MT1-MMP proteolysis of PTK7 in cell functions. Our data also demonstrate that a fine balance between the metalloproteinase activity and PTK7 levels is required for normal development of zebrafish (Danio rerio). Aberration of this balance by the proteinase inhibition or PTK7 silencing results in the PCP-dependent convergent extension defects in the zebrafish. Overall, our data suggest that the MT1-MMP-PTK7 axis plays an important role in both cancer cell invasion and normal embryogenesis in vertebrates. Further insight into these novel mechanisms may promote understanding of directional cell motility and lead to the identification of therapeutics to treat PCP-related developmental disorders and malignancy.
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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.