ArticleOncogene2021
Epigenetic induction of lipocalin 2 expression drives acquired resistance to 5-fluorouracil in colorectal cancer through integrin β3/SRC pathway.
Article in Oncogene, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
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Who cites it
21 citing papers in PubMed, 27 citations in OpenAlex.
- Article
- Targeting EHMT2 overcomes 5-fluorouracil resistance in colorectal cancer by modulating cell cycle and apoptosis.Signal transduction and targeted therapy · 2026Article
- The Molecular and Functional Landscape of Resistance to FOLFIRI Chemotherapy in Metastatic Colorectal Cancer.Cancer discovery · 2026Article
- Beyond olfaction: New insights into human odorant binding proteins.Protein science : a publication of the Protein Society · 2026Review
- ZCCHC4 Orchestrates Hepatocellular Carcinoma Metastasis by Regulating Lipid biosynthesis and TMEM97/LCN2/Twist1 Pathway.International journal of biological sciences · 2026Article
- Integrated transcriptomics-metabolomics analysis reveals biomarkers and metabolic dysregulation characteristics of parenteral nutrition-associated liver disease.Frontiers in nutrition · 2026Article
- LCN2 promotes focal adhesion formation and invasion by stimulating c-Src activation.Journal of cell science · 2025Article
- Integrins in Cancer Drug Resistance: Molecular Mechanisms and Clinical Implications.International journal of molecular sciences · 2025Review
- Cytoglobin suppresses oxidative damage and compensatory proliferation via inhibiting AKT/ERK1/2/CyclinD1 axis in hepatocellular carcinoma.American journal of cancer research · 2025Article
- Identification of SLC22A17 DNA methylation hotspot as a potential biomarker in cutaneous melanoma.Journal of translational medicine · 2024Article
- HIF-1α Pathway Orchestration by LCN2: A Key Player in Hypoxia-Mediated Colitis Exacerbation.Inflammation · 2024Article
- Identification of the biological functions and chemo-therapeutic responses of ITGB superfamily in ovarian cancer.Discover oncology · 2024Article
- Silencing LCN2 suppresses oral squamous cell carcinoma progression by reducing EGFR signal activation and recycling.Journal of experimental & clinical cancer research : CR · 2023Article
- Multiomics of Colorectal Cancer Organoids Reveals Putative Mediators of Cancer Progression Resulting from SMAD4 Inactivation.Journal of proteome research · 2023Article
- Construction of a DDR-related signature for predicting of prognosis in metastatic colorectal carcinoma.Frontiers in oncology · 2023Article
- Iron metabolism in colorectal cancer.Frontiers in oncology · 2023Review
- A CRISPR Path to Finding Vulnerabilities and Solving Drug Resistance: Targeting the Diverse Cancer Landscape and Its Ecosystem.Advanced genetics (Hoboken, N.J.) · 2022Review
- Transcriptomic and Proteomic Profiles for Elucidating Cisplatin Resistance in Head-and-Neck Squamous Cell Carcinoma.Cancers · 2022Article
- Article
- Bioinformatic analysis of theFrontiers in cell and developmental biology · 2022Article
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The therapeutic efficacy of 5-fluorouracil (5-FU) is often reduced by the development of drug resistance. We observed significant upregulation of lipocalin 2 (LCN2) expression in a newly established 5-FU-resistant colorectal cancer (CRC) cell line. In this study, we demonstrated that 5-FU-treated CRC cells developed resistance through LCN2 upregulation caused by LCN2 promoter demethylation and that feedback between LCN2 and NF-κB further amplified LCN2 expression. High LCN2 expression was associated with poor prognosis in CRC patients. LCN2 attenuated the cytotoxicity of 5-FU by activating the SRC/AKT/ERK-mediated antiapoptotic program. Mechanistically, the LCN2-integrin β3 interaction enhanced integrin β3 stability, thus recruiting SRC to the cytomembrane for autoactivation, leading to downstream AKT/ERK cascade activation. Targeting LCN2 or SRC compromised the growth of CRC cells with LCN2-induced 5-FU resistance. Our findings demonstrate a novel mechanism of acquired resistance to 5-FU, suggesting that LCN2 can be used as a biomarker and/or therapeutic target for advanced CRC.
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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.