ArticleCell & bioscience2022
IFITM3 promotes malignant progression, cancer stemness and chemoresistance of gastric cancer by targeting MET/AKT/FOXO3/c-MYC axis.
Article in Cell & bioscience, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 29 citations in OpenAlex.
- Bone Tumor Microenvironment Is Associated with Meningioma Enlargement and Inflammatory Transcriptional States: A Candidate Role for Macrophage-Derived IL-1β.Biomedicines · 2026Article
- Interferon-induced transmembrane (IFITM) proteins at the tumour-immune interface: A four-axis framework for their context-dependent roles.Clinical and translational medicine · 2026Review
- Interferon-induced transmembrane proteins in cancer and virus biology: a membrane perspective.mBio · 2026Review
- IFITM3 promotes an M2-like tumor-supportive microenvironment in acute myeloid leukemia.Medical oncology (Northwood, London, England) · 2026Article
- Interferon-induced transmembrane proteins: membrane gatekeepers of fusion and infection.Frontiers in cellular and infection microbiology · 2026Review
- Targeted nanoparticle-mediated Co-delivery of IFITM3 KO and ponatinib reverses TKI resistance in chronic myeloid leukemia.Frontiers in pharmacology · 2026Article
- IFITM3-MET interaction drives osimertinib resistance through AKT pathway activation in EGFR-mutant non-small cell lung cancer.Molecular cancer · 2025Article
- IFITM3 enhances immunosensitivity via MHC-I regulation and is associated with the efficacy of anti-PD-1/-L1 therapy in SCLC.Molecular cancer · 2025Article
- A 3D Self-Assembly Platform Integrating Decellularized Matrix Recapitulates In Vivo Tumor Phenotypes and Heterogeneity.Cancer research · 2025Article
- Development and synthesis of diffractaic acid analogs as potent inhibitors of colorectal cancer stem cell traits.Scientific reports · 2025Article
- A spatially resolved single-cell landscape of colorectal cancer liver metastasis reveals a stromal-tumor glycolytic signaling interaction.Frontiers in cell and developmental biology · 2025Article
- Attenuation of IFITM proteins' antiviral activity through sequestration into intraluminal vesicles of late endosomes.Frontiers in immunology · 2025Article
- c-Myc and FOXO3a-The Everlasting Decision Between Neural Regeneration and Degeneration.International journal of molecular sciences · 2024Review
- ISL1 and AQP5 complement each other to enhance gastric cancer cell stemness by regulating CD44 expression.Translational cancer research · 2024Article
- Article
- Ferroptosis regulating lipid peroxidation metabolism in the occurrence and development of gastric cancer.World journal of gastrointestinal oncology · 2024Article
- Engineering Tumor Stroma Morphogenesis Using Dynamic Cell-Matrix Spheroid Assembly.bioRxiv : the preprint server for biology · 2024Article
- IFITM3 promotes glioblastoma stem cell-mediated angiogenesis via regulating JAK/STAT3/bFGF signaling pathway.Cell death & disease · 2024Article
- CCL16 is a pro-tumor chemokine that recruits monocytes and macrophages to promote hepatocellular carcinoma progression.American journal of cancer research · 2024Article
- RNASE4 promotes malignant progression and chemoresistance in hypoxic glioblastoma via activation of AXL/AKT and NF-κB/cIAPs signaling pathways.American journal of cancer research · 2024Article
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Authors and funding
13 authors at 8 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundTargeting the HGF/MET signaling pathway has been a viable therapeutic strategy for various cancer types due to hyperactivation of HGF/MET axis occurs frequently that leads to detrimental cancer progression and recurrence. Deciphering novel molecule mechanisms underlying complex HGF/MET signaling network is therefore critical to development of effective therapeutics for treating MET-dependent malignancies.
resultsUsing isobaric mass tag-based quantitative proteomics approach, we identified IFITM3, an interferon-induced transmembrane protein that was highly expressed in micro-dissected gastric cancer (GC) tumor regions relative to adjacent non-tumor epithelia. Analyses of GC clinical specimens revealed that expression IFITM3 was closely correlated to advanced pathological stages. IFITM3 has been reported as a PIP3 scaffold protein that promotes PI3K signaling. In present study, we unprecedentedly unraveled that IFITM3 associated with MET and AKT to facilitate HGF/MET mediated AKT signaling crosstalk in suppressing FOXO3, consequently leading to c-MYC mediated GC progression. In addition, gene ontology analyses of the clinical GC cohort revealed significant correlation between IFITM3-associated genes and targets of c-MYC, which is a crucial downstream effector of HGF/MET pathway in cancer progression. Moreover, we demonstrated ectopic expression of IFITM3 suppressed FOXO3 expression, consequently led to c-MYC induction to promote tumor growth, cell metastasis, cancer stemness as well as chemoresistance. Conversely, depletion of IFITM3 resulted in suppression of HGF triggered cellular growth and migration via inhibition of AKT/c-MYC signaling in GC.
conclusionsIn summary, our present study unveiled a novel regulatory mechanism for c-MYC-driven oncogenesis underlined by IFITM3-mediated signaling crosstalk between MET associated AKT signaling cascade.
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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.