ArticleOncogene2012
P38MAPK is a major determinant of the balance between apoptosis and autophagy triggered by 5-fluorouracil: implication in resistance.
Article in Oncogene, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 73 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
73 citing papers in PubMed, 1 synthesis or guideline pooled it, 115 citations in OpenAlex.
- ATM is associated with the prognosis of colorectal cancer: a systematic review.Frontiers in oncology · 2025Pooled it
- Mitochondrial Deoxyguanosine Kinase Induces 5-Fluorouracil Chemotherapy Sensitivity through Autophagy.Current cancer drug targets · 2025Article
- Synergistic Potential of Argentatins A and B to Improve 5-Fluorouracil Cytotoxicity in Colorectal Cancer Cell Models.Journal of cellular and molecular medicine · 2024Article
- DUSP6 regulates Notch1 signalling in colorectal cancer.Nature communications · 2024Article
- Resveratrol as sensitizer in colorectal cancer plasticity.Cancer metastasis reviews · 2024Review
- Article
- Cell Death, by Any Other Name….Cells · 2024Review
- SIRT1 promotes the progression and chemoresistance of colorectal cancer through the p53/miR-101/KPNA3 axis.Cancer biology & therapy · 2023Article
- Natural Compounds Targeting the Autophagy Pathway in the Treatment of Colorectal Cancer.International journal of molecular sciences · 2023Review
- P38 MAPK and Radiotherapy: Foes or Friends?Cancers · 2023Review
- Review of 5-FU resistance mechanisms in colorectal cancer: clinical significance of attenuated on-target effects.Cancer drug resistance (Alhambra, Calif.) · 2023Review
- Article
- Review
- ECM1 regulates the resistance of colorectal cancer to 5-FU treatment by modulating apoptotic cell death and epithelial-mesenchymal transition induction.Frontiers in pharmacology · 2022Article
- Autophagy: A Versatile Player in the Progression of Colorectal Cancer and Drug Resistance.Frontiers in oncology · 2022Review
- Article
- Protective autophagy by thymidine causes resistance to rapamycin in colorectal cancer cellsCancer drug resistance (Alhambra, Calif.) · 2021Article
- Canonical and Non-canonical TGFβ Signaling Activate Autophagy in an ULK1-Dependent Manner.Frontiers in cell and developmental biology · 2021Article
- USP11 induce resistance to 5-Fluorouracil in Colorectal Cancer through activating autophagy by stabilizing VCP.Journal of Cancer · 2021Article
- Pharmacogenomics of 5-fluorouracil in colorectal cancer: review and update.Cellular oncology (Dordrecht, Netherlands) · 2020Review
13 more citing papers are in PubMed but not listed here.
Corrections and comments
- Retraction · 2024-03-05Concerns/Issues about Image · Duplication of/in Image · Error in Image · Euphemisms for Duplication · Objections by Author(s) · Original Data and/or Images not Provided and/or not Available · Unreliable Data ·
- Retracted
Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
5-Fluorouracil (5-FU), together with other drugs such as oxaliplatin, is one of the most important pharmacological agents in the treatment of colorectal cancer. Although mitogen-activated protein kinases (MAPKs) have been extensively connected with resistance to platinum compounds, no role has been established in 5-FU resistance. Here we demonstrate that p38MAPK activation is a key determinant in the cellular response to 5-FU. Thus, inhibition of p38MAPKα by SB203580 compound or by short-hairpin RNA interference-specific knockdown correlates with a decrease in the 5-FU-associated apoptosis and chemical resistance in both HaCaT and HCT116 cells. Activation of p38MAPK by 5-FU was dependent on canonical MAP2K, MAPK kinase (MKK)-3 and MKK6. In addition, ataxia telangiectasia mutated (ATM) and ataxia telangiectasia and Rad3 related (ATR) showed a redundancy of function for the final activation of p38MAPK. Resistance associated with p38MAPK inhibition correlates with an autophagic response that was mediated by a decrease in p53-driven apoptosis, without effect onto p53-dependent autophagy. Moreover, the results with colorectal cancer-derived cell lines with different p53 status and patterns of resistance to 5-FU suggest that de novo and acquired resistance was controlled by similar mechanisms. In summary, our data demonstrate a critical role for the p38MAPK signaling pathway in the cellular response to 5-FU by controlling the balance between apoptosis and autophagy.
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What OpenQuestion holds
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.