ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2024
MAPK Signaling-Mediated RFNG Phosphorylation and Nuclear Translocation Restrain Oxaliplatin-Induced Apoptosis and Ferroptosis.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed.
- PUM2 inhibits ferroptosis and enhances oxaliplatin resistance in COAD via the NEDD4L/NRF2 axis.Translational oncology · 2026Article
- An Intravesical Akkermansia muciniphila-Based Chemo-Immunotherapeutic Platform for Bladder Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Quercetin ameliorates aflatoxin BJournal of animal science and biotechnology · 2026Article
- [Tumor-secreted dentin sialophosphoprotein induces oxaliplatin resistance in colorectal cancer through an integrin αvβ3-dependent pathway].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2026Article
- Targeting post-translational modifications: novel insights into bone metabolic diseases.Journal of advanced research · 2026Review
- Forchlorfenuron Exposure Induces Hepatocyte Apoptosis via MKK3/P38/ATF2 Pathway.International journal of molecular sciences · 2026Article
- Atlas-Guided Nanocarrier Strategies Targeting Spatial NTRK2/MAPK Signaling in EGFR-TKI-Resistant Niches of Esophageal Squamous Cell Carcinoma.Pharmaceutics · 2026Review
- Ultrasound-Propelled ferroptosis catalytic amplification for Active-targeting sonodynamic anti-tumor therapy with Concurrent Photoacoustic/MRI visualization.Ultrasonics sonochemistry · 2026Article
- Cancer Cell Dormancy and Chemotherapy Resistance.Journal of Cancer · 2026Review
- Nuclear-Cytoplasmic Axis in Cancer: From Protein Mislocalization to Anticancer Drug Resistance.Oncology research · 2026Review
- Exportin 1 inhibitor KPT‑330 reverses oxaliplatin resistance via p53 nuclear retention in colorectal cancer.International journal of molecular medicine · 2026Article
- Immunoregulatory roles of post-translational modifications in colorectal cancer: mechanisms and therapeutic implications.Cellular and molecular life sciences : CMLS · 2025Review
- Ubiquitin-specific protease 13 promotes colorectal cancer progression by stabilizing mitogen-activated protein kinase kinase 3.Molecular biomedicine · 2025Article
- [Elevated TMCO1 expression in gastric cancer is associated poor prognosis and promotes malignant phenotypes of tumor cells by inhibiting apoptosis].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2025Article
- Targeting ferroptosis and cuproptosis in gastrointestinal cancers: molecular mechanisms, metabolic vulnerabilities, and therapeutic interventions.Molecular biomedicine · 2025Review
- EPS8L2 drives colorectal cancer cell proliferation and migration via YBX1-dependent activation of G3BP2 transcription.Cell death & disease · 2025Article
- PRDX1 knockdown promotes erastin-induced ferroptosis and impedes diffuse large B-cell lymphoma development by inhibiting the MAPK/ERK pathway.BMC cancer · 2025Article
- Targeting PTGDS Promotes ferroptosis in peripheral T cell lymphoma through regulating HMOX1-mediated iron metabolism.British journal of cancer · 2025Article
- Harnessing ferroptosis for precision oncology: challenges and prospects.BMC biology · 2025Review
- Single-cell and spatial-resolved profiling reveals cancer-associated fibroblast heterogeneity in colorectal cancer metabolic subtypes.Journal of translational medicine · 2025Article
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9 authors.
Funding
Abstract
Chemotherapy resistance remains a major challenge in the treatment of colorectal cancer (CRC). Therefore, it is crucial to develop novel strategies to sensitize cancer cells to chemotherapy. Here, the fringe family is screened to determine their contribution to chemotherapy resistance in CRC. It is found that RFNG depletion significantly sensitizes cancer cells to oxaliplatin treatment. Mechanistically, chemotherapy-activated MAPK signaling induces ERK to phosphorylate RFNG Ser255 residue. Phosphorylated RFNG S255 (pS255) interacts with the nuclear importin proteins KPNA1/importin-α1 and KPNB1/importin-β1, leading to its translocation into the nucleus where it targets p53 and inhibits its phosphorylation by competitively inhibiting the binding of CHK2 to p53. Consequently, the expression of CDKN1A is decreased and that of SLC7A11 is increased, leading to the inhibition of apoptosis and ferroptosis. In contrast, phosphor-deficient RFNG S225A mutant showed increased apoptosis and ferroptosis, and exhibited a notable response to oxaliplatin chemotherapy both in vitro and in vivo. It is further revealed that patients with low RFNG pS255 exhibited significant sensitivity to oxaliplatin in a patient-derived xenograft (PDX) model. These findings highlight the crosstalk between the MAPK and p53 signaling pathways through RFNG, which mediates oxaliplatin resistance in CRC. Additionally, this study provides guidance for oxaliplatin treatment of CRC patients.
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