ArticleMolecular therapy : the journal of the American Society of Gene Therapy2018
RTN4 Knockdown Dysregulates the AKT Pathway, Destabilizes the Cytoskeleton, and Enhances Paclitaxel-Induced Cytotoxicity in Cancers.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 48 citations in OpenAlex.
- Review
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- Targeting Reticulin 4 (RTN4) Within Small Extracellular Vesicles Combats Metastasis and Reinforces Immunotherapy in Triple-Negative Breast Cancer.Journal of extracellular vesicles · 2025Article
- Identification of Nogo-B as a potential therapeutic target of osteosarcoma via stereochemically selective covalent probes.Cell death & disease · 2025Article
- Spatiotemporal Profiling Defines Persistence and Resistance Dynamics during Targeted Treatment of Melanoma.Cancer research · 2025Article
- The Overexpression of RTN4 Significantly Associated With an Unfavourable Prognosis in Patients With Lower-Grade Gliomas.Journal of cellular and molecular medicine · 2025Article
- Modification-specific Proteomic Analysis Reveals Cysteine S-Palmitoylation Involved in Esophageal Cancer Cell Radiation.ACS omega · 2025Article
- Unraveling the causal relationship and potential mechanisms between osteoarthritis and breast cancer: insights from mendelian randomization and bioinformatics analysis.Discover oncology · 2024Article
- Increased levels of versican and insulin-like growth factor 1 in peritumoral mammary adipose tissue are related to aggressiveness in estrogen receptor-positive breast cancer.Molecular medicine (Cambridge, Mass.) · 2024Article
- NLRC5 promotes tumorigenesis by regulating the PI3K/AKT signaling pathway in cervical cancer.Scientific reports · 2024Article
- Ceramides are fuel gauges on the drive to cardiometabolic disease.Physiological reviews · 2024Review
- Proteomic Identification of Small Extracellular Vesicle Proteins LAMB1 and Histone H4 for Prostate Cancer Diagnosis and Risk Stratification.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Exploring Hypertrophic Cardiomyopathy Biomarkers through Integrated Bioinformatics Analysis: Uncovering Novel Diagnostic Candidates.Cardiology research and practice · 2024Article
- The Reticulon-4 3-bp Deletion/Insertion Polymorphism Is Associated with Structural mRNA Changes and the Risk of Breast Cancer: A Population-Based Case-Control Study with Bioinformatics Analysis.Life (Basel, Switzerland) · 2023Article
- The Clinical and Biological Effects of Receptor Expression-Enhancing Protein 6 in Tongue Squamous Cell Carcinoma.Biomedicines · 2023Article
- The risk model construction of the genes regulated by H3K36me3 and H3K79me2 in breast cancer.Biophysics reports · 2023Article
- Comparative Proteomics Analysis of Exosomes Identifies Key Pathways and Protein Markers Related to Breast Cancer Metastasis.International journal of molecular sciences · 2023Article
- New Transcriptomic Biomarkers of 5-Fluorouracil Resistance.International journal of molecular sciences · 2023Article
- MicroRNA and mRNA Expression Changes in Glioblastoma Cells Cultivated under Conditions of Neurosphere Formation.Current issues in molecular biology · 2022Article
- Interoperability of RTN1A in dendrite dynamics and immune functions in human Langerhans cells.eLife · 2022Article
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Reticulon-4 (RTN4), commonly known as a neurite outgrowth inhibitor (Nogo), is emerging as an important player in human cancers. Clinically, we found lower RTN4 expression in patient-derived tumors was associated with significantly better survival in lung, breast, cervical, and renal cancer patients. To identify the role of RTN4 in cancer biology, we performed mass spectrometry-based quantitative proteomic analysis on cancer cells following RTN4 knockdown and found its link with pro-survival as well as cytoskeleton-related processes. Subsequent mechanistic investigations revealed that RTN4 regulates lipid homeostasis, AKT signaling, and cytoskeleton modulation. In particular, downregulation of RTN4 reduced sphingomyelin synthesis and impaired plasma membrane localization of AKT, wherein AKT phosphorylation, involved in many cancers, was significantly reduced without any comparable effect on AKT-related upstream kinases, in a sphingolipid-dependent manner. Furthermore, knockdown of RTN4 retarded proliferation of cancer cells in vitro as well as tumor xenografts in mice. Finally, RTN4 knockdown affected tubulin stability and promoted higher cytotoxic effects with chemotherapeutic paclitaxel in cancer cells both in vitro and in vivo. In summary, RTN4 is involved in carcinogenesis and represents a molecular candidate that may be targeted to achieve desired antitumor effects in clinics.
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