ArticleOncotarget2016
FoxO3a confers cetuximab resistance in RAS wild-type metastatic colorectal cancer through c-Myc.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
17 citing papers in PubMed, 25 citations in OpenAlex.
- Triggering SORL1 Expression Restricts ccRCC Progression by Inducing Ubiquitination-Mediated c-Myc Degradation.Cancer science · 2026Article
- Ferroptosis suppression by MYC confers oxaliplatin resistance in colorectal cancer via FTH1 and GPX4.Cancer chemotherapy and pharmacology · 2026Article
- Comprehensive Genomic Profiling of Advanced Anal Adenocarcinoma in Japan.JCO precision oncology · 2026Article
- The cell autonomous and non-autonomous functions of Rab27 in longevity and neuroprotection inAutophagy · 2025Article
- Asparaginyl endopeptidase contributes to cetuximab resistance via MEK/ERK signaling in RAS wide-type metastatic colorectal cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2023Article
- Significant position of C-myc in colorectal cancer: a promising therapeutic target.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2022Review
- Control of Oxidative Stress in Cancer Chemoresistance: Spotlight on Nrf2 Role.Antioxidants (Basel, Switzerland) · 2021Review
- Abnormal Expression of Mitochondrial Ribosomal Proteins and Their Encoding Genes with Cell Apoptosis and Diseases.International journal of molecular sciences · 2020Review
- c-MYC Expression Is a Possible Keystone in the Colorectal Cancer Resistance to EGFR Inhibitors.Cancers · 2020Article
- Article
- Population and single‑cell transcriptome analyses reveal diverse transcriptional changes associated with radioresistance in esophageal squamous cell carcinoma.International journal of oncology · 2019Article
- Review
- FOXO3 on the Road to Longevity: Lessons From SNPs and Chromatin Hubs.Computational and structural biotechnology journal · 2019Review
- MALDI-MSI of Immunotherapy: Mapping the EGFR-Targeting Antibody Cetuximab in 3D Colon-Cancer Cell Cultures.Analytical chemistry · 2018Article
- The Dominant Role of Forkhead Box Proteins in Cancer.International journal of molecular sciences · 2018Review
- Uncoupling FoxO3A mitochondrial and nuclear functions in cancer cells undergoing metabolic stress and chemotherapy.Cell death & disease · 2018Article
- PLOD2 regulated by transcription factor FOXA1 promotes metastasis in NSCLC.Cell death & disease · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Resistance to epidermal growth factor receptor (EGFR) targeted monoclonal antibody therapy represents a clinical challenge in patients suffered from RAS wild-type (WT) metastatic colorectal cancer (mCRC). However, the molecular mechanisms and key factors conferring this resistance are largely unknown. Forkhead transcription factors of the O class 3a (FoxO3a), an important regulator of cell survival, has been reported with dual functions in tumor recently. In this study, we found that FoxO3a was highly expressed in cetuximab resistant CRC tissues compared with cetuximab sensitive tissues. We therefore further analyzed its function in induced cetuximab resistant RAS-WT CRC cells (Caco2-CR) and intrinsic resistant cells with BRAF mutation (HT29). We found that FoxO3a was significantly up-regulated in Caco2-CR as well as in cetuximab treated HT29 cells. Knockdown of FoxO3a could sensitize these cells to cetuximab treatment with reduced cell proliferation and migration ability. Further, biochemical experiments demonstrated that FoxO3a directly bind to c-Myc promoter and activated the transcription of the c-Myc gene, thus participated in regulating of c-Myc downstream genes, including ACO2, LARS2, MRPL12 and PKM2 in these resistant cells. Moreover, knockdown of c-Myc elevated cell apoptosis to cetuximab treatment and suppressed cell proliferation and migration ability consistently. Altogether, our study indicates that FoxO3a might be a key regulator in cetuximab resistance through up-regulating c-Myc in colorectal cancer targeted therapy.
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Registered trials
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.