ArticleCancer research2016
Targeting the WASF3-CYFIP1 Complex Using Stapled Peptides Suppresses Cancer Cell Invasion.
Article in Cancer research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 67 citations in OpenAlex.
- Targeting the WASF3 Regulatory Complex in Pancreatic Cancer Using Stapled Peptides.Biochemistry · 2026Article
- Molecular Mechanisms of FAT Atypical Cadherin 1 (FAT1), the Hippo Pathway, and the Yes-Associated Protein (YAP) Signaling Pathways in Some Cancers.Asian Pacific journal of cancer prevention : APJCP · 2026Review
- The Role of Actin-Binding Proteins in Breast Cancer Progression.Breast cancer (Dove Medical Press) · 2026Review
- Development of an All-Hydrocarbon Stapled Peptide Targeting BRK1 in Triple-Negative Breast Cancer.ACS medicinal chemistry letters · 2025Article
- From Concepts to Inhibitors: A Blueprint for Targeting Protein-Protein Interactions.Chemical reviews · 2025Review
- The Potential of Peptide-Based Inhibitors in Disrupting Protein-Protein Interactions for Targeted Cancer Therapy.International journal of molecular sciences · 2025Review
- CYFIP1 coordinate with RNMT to induce osteosarcoma cuproptosis via AURKAIP1 m7G modification.Molecular medicine (Cambridge, Mass.) · 2025Article
- PSIP1 promotes gefitinib resistance in lung adenocarcinoma by inducing the expression of WASF3 and its downstream ITGB3/AKT signaling.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025Article
- Tackling Undruggable Targets with Designer Peptidomimetics and Synthetic Biologics.Chemical reviews · 2024Review
- Article
- Identification of small molecules that suppress cell invasion and metastasis promoted by WASF3 activation.Heliyon · 2023Article
- The WAVE3/β-catenin oncogenic signaling regulates chemoresistance in triple negative breast cancer.Breast cancer research : BCR · 2023Article
- Mitochondrial regulator ATAD3A: a molecular determinant favoring head and neck cancer development.Oncoscience · 2023Article
- Comprehensive Analysis of m7G-Related Genes and Chronic Hepatitis B: Diagnostic Markers, Immune Microenvironment Regulation, Disease Progression.Journal of immunology research · 2023Article
- The diverse functions of FAT1 in cancer progression: good, bad, or ugly?Journal of experimental & clinical cancer research : CR · 2022Review
- Targeting the WASF3 complex to suppress metastasis.Pharmacological research · 2022Review
- Article
- ATAD3A mediates activation of RAS-independent mitochondrial ERK1/2 signaling, favoring head and neck cancer development.Journal of experimental & clinical cancer research : CR · 2022Article
- Design of Protein Segments and Peptides for Binding to Protein Targets.Biodesign research · 2022Review
- m7G Methylation-Related Genes as Biomarkers for Predicting Overall Survival Outcomes for Hepatocellular Carcinoma.Frontiers in bioengineering and biotechnology · 2022Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Activation of the WASF3 protein by extracellular stimuli promotes actin cytoskeleton reorganization and facilitates cancer cell invasion, whereas WASF3 depletion suppresses invasion and metastasis. In quiescent cells, the interaction between WASF3 and a complex of proteins, including CYFIP1, acts as a conformational restraint to prevent WASF3 activation. Therefore, we took advantage of this endogenous regulatory mechanism to investigate potential sites that disrupt WASF3 function. Here, we show that genetic knockdown of CYFIP1 in cancer cells led to the destabilization of the WASF3 complex, loss of WASF3 function, and suppressed invasion. Based on existing crystallographic data, we developed stapled peptides, referred to as WASF Helix Mimics (WAHM), that target an α-helical interface between WASF3 and CYFIP1. Treatment of highly invasive breast and prostate cancer cells with WAHM inhibitor peptides significantly reduced motility and invasion in vitro. Mechanistic investigations revealed that these inhibitors suppressed the interaction between Rac and the WASF3 complex, which has been shown to promote cell migration. Furthermore, peptide-mediated inhibition of WASF3 also resulted in the dysregulation of known downstream targets such as MMP-9 and KISS1. Finally, we demonstrate that this invasive phenotype is specific to WASF3 as depletion of WASF1 and WASF2, which can also bind to CYFIP1, did not affect invasion. Collectively, our findings suggest that targeting WASF3 function with WAHM peptides could represent a promising therapeutic strategy for preventing tumor invasion and metastasis.
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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.