ArticleCancer research2022
WNT5A-RHOA Signaling Is a Driver of Tumorigenesis and Represents a Therapeutically Actionable Vulnerability in Small Cell Lung Cancer.
Article in Cancer research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 14 citations in OpenAlex.
- Review
- An evolutionarily conserved salt bridge stabilizes the active site for GTP hydrolysis in Rho GTPases.The Journal of biological chemistry · 2026Article
- RHOA at the intersection of inflammation-driven and sporadic colorectal cancer.Frontiers in immunology · 2026Review
- Wnt signaling pathways in biology and disease: mechanisms and therapeutic advances.Signal transduction and targeted therapy · 2025Review
- HucMSCs-derived Exosomes Promote Lung Development in Premature Birth via Wnt5a/ROCK1 Axis.Stem cell reviews and reports · 2025Article
- Bone Marrow Mesenchymal Stem Cells-Derived Exosomes Inhibit Apoptosis of Pulmonary Microvascular Endothelial Cells in COPD Mice Through miR-30b/Wnt5a Pathway.International journal of nanomedicine · 2025Article
- Emerging roles and biomarker potential of WNT6 in human cancers.Cell communication and signaling : CCS · 2024Review
- RhoA-ROCK2 signaling possesses complex pathophysiological functions in cancer progression and shows promising therapeutic potential.Cancer cell international · 2024Review
- Application of urine proteomics in the diagnosis and treatment effectiveness monitoring of early-stage Mycosis Fungoides.Clinical proteomics · 2024Article
- Review
- Therapeutic targeting of voltage-gated sodium channel NaFrontiers in pharmacology · 2024Review
- Actionable Driver Events in Small Cell Lung Cancer.International journal of molecular sciences · 2023Review
- Altered binding affinity of SIX1-Q177R correlates with enhanced WNT5A and WNT pathway effector expression in Wilms tumor.Disease models & mechanisms · 2023Article
- The New Way to Define Key Oncogenic Drivers of Small Cell Lung Cancer.Development & reproduction · 2023Article
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 2 countries.
Funding
Abstract
WNT signaling represents an attractive target for cancer therapy due to its widespread oncogenic role. However, the molecular players involved in WNT signaling and the impact of their perturbation remain unknown for numerous recalcitrant cancers. Here, we characterize WNT pathway activity in small cell lung cancer (SCLC) and determine the functional role of WNT signaling using genetically engineered mouse models. β-Catenin, a master mediator of canonical WNT signaling, was dispensable for SCLC development, and its transcriptional program was largely silenced during tumor development. Conversely, WNT5A, a ligand for β-catenin-independent noncanonical WNT pathways, promoted neoplastic transformation and SCLC cell proliferation, whereas WNT5A deficiency inhibited SCLC development. Loss of p130 in SCLC cells induced expression of WNT5A, which selectively increased Rhoa transcription and activated RHOA protein to drive SCLC. Rhoa knockout suppressed SCLC development in vivo, and chemical perturbation of RHOA selectively inhibited SCLC cell proliferation. These findings suggest a novel requirement for the WNT5A-RHOA axis in SCLC, providing critical insights for the development of novel therapeutic strategies for this recalcitrant cancer. This study also sheds light on the heterogeneity of WNT signaling in cancer and the molecular determinants of its cell-type specificity. SIGNIFICANCE: The p130-WNT5A-RHOA pathway drives SCLC progression and is a potential target for the development of therapeutic interventions and biomarkers to improve patient treatment.
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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 Socratic graph.