ArticleTherapeutic advances in medical oncology2021
NDUFA4L2 promotes trastuzumab resistance in HER2-positive breast cancer.
Article in Therapeutic advances in medical oncology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 22 citations in OpenAlex.
- NDUFA4L2 rescues hyperoxia-induced migration defects in retinal endothelial cells by reversing isocitrate dehydrogenase flux blockade.bioRxiv : the preprint server for biology · 2026Article
- Integrating weighted gene co-expression network analysis and machine learning reveal that NDUFA4L2 alleviates KA-induced HT22 cell neurotoxicity, apoptosis, oxidative stress, and mitochondrial dysfunction.Journal of bioenergetics and biomembranes · 2026Article
- NDUFA4L2 regulates the progression and chemotherapy sensitivity of HNSCC by inhibiting PANoptosis.NPJ precision oncology · 2026Article
- Trastuzumab-Conjugated Nanoliposomes for Targeted Capecitabine Delivery to Suppress HER2-Positive Breast Tumor: Efficacy Analysis in NOD SCID Mice Xenografts.International journal of nanomedicine · 2026Article
- Diagnostic and prognostic values of differentially expressed genes in canine mammary carcinoma: An integrated bioinformatics analysis.PloS one · 2026Article
- Ectopic expression of GDF15 in cancer-associated fibroblasts enhances melanoma immunosuppression via the GFRAL/RET cascade.Journal for immunotherapy of cancer · 2025Article
- Nucleotide metabolism-associated drug resistance gene NDUFA4L2 promotes colon cancer progression and 5-FU resistance.Scientific reports · 2025Article
- Identification of CAF signature genes and construction of CAF-based risk signature in hepatocellular carcinoma by multi-omics analysis.Frontiers in immunology · 2025Article
- Targeting Glycolysis for Treatment of Breast Cancer Resistance: Current Progress and Future Prospects.International journal of biological sciences · 2025Review
- Metabolic reprogramming and therapeutic resistance in primary and metastatic breast cancer.Molecular cancer · 2024Review
- Single-cell RNA sequencing elucidated the landscape of breast cancer brain metastases and identified ILF2 as a potential therapeutic target.Cell proliferation · 2024Article
- Pancancer analysis of NDUFA4L2 with focused role in tumor progression and metastasis of colon adenocarcinoma.Medical oncology (Northwood, London, England) · 2024Article
- Promoting reactive oxygen species accumulation to overcome tyrosine kinase inhibitor resistance in cancer.Cancer cell international · 2024Review
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- Hypoxia-induced the upregulation of NDUFA4L2 promoted colon adenocarcinoma progression through ROS-mediated PI3K/AKT pathway.Cytotechnology · 2023Article
- Transcriptional regulation of NDUFA4L2 by NFIB induces sorafenib resistance by decreasing reactive oxygen species in hepatocellular carcinoma.Cancer science · 2023Article
- Inactivating Amplified HER2: Challenges, Dilemmas, and Future Directions.Cancer research · 2022Article
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- MiR-98-5p/IGF2 Axis Influence Herceptin Sensitivity through IGF1R/HER2 Heterodimer Formation and AKT/mTOR Signal Pathway in HER2 Positive Breast Cancer.Asian Pacific journal of cancer prevention : APJCP · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundTrastuzumab (Herceptin) is the key systemic therapy for HER2-positive breast cancer. However, the initial response rate is limited to approximately 50% in patients. Moreover, most patients, especially at an advanced stage, eventually develop acquired resistance. Understanding the mechanisms of trastuzumab resistance is crucial for achieving better treatment outcome in this group of patients.
methodsA trastuzumab-resistant (TR) cell line was developed using the BT474 HER2-positive breast cancer cell line. Whole-transcriptome expression array was performed and the TR-related gene NDUFA4L2 was identified by differential expression analysis between BT474 and BT474-TR. Mitochondrial localization of NDUFA4L2 was confirmed by immunofluorescence and western blotting using mitochondrial fractionation. Mitochondrial function and energy metabolism were evaluated using Seahorse, ATP production, and lactate production assays, and cellular reactive oxygen species (ROS) levels were determined using DCFDA. NDUFA4L2 expression in patients was evaluated by immunohistochemistry, and relapse-free survival was analyzed using the Kaplan-Meier method.
resultsNDUFA4L2 was highly expressed in the TR HER2-positive breast cancer cell line. High expression level of NDUFA4L2 was associated with shorter relapse-free intervals in trastuzumab-treated HER2-positive breast cancer patients. Overexpression of NDUFA4L2 enhanced Warburg effects, enhanced aerobic glycolysis, reduced oxygen consumption, and lowered ROS production. Mechanistically, overexpression of NDUFA4L2 facilitated mitochondrial relocalization of HER2 and suppressed ROS production, thus rendering cancer cells more resistant to trastuzumab treatment.
conclusionsWe identified NDUFA4L2 as a new biomarker and potential therapeutic target for TR HER2-positive breast cancer.
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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.