ArticleBritish journal of cancer2017
Loss of CUL4A expression is underlying cisplatin hypersensitivity in colorectal carcinoma cells with acquired trabectedin resistance.
Article in British journal of cancer, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 16 citations in OpenAlex.
- KDM5D expression is lost in cisplatin‑resistant neuroblastoma cells.Oncology reports · 2026Article
- CUL4A silencing attenuates cervical carcinogenesis and improves Cisplatin sensitivity.Molecular and cellular biochemistry · 2024Article
- Paraptotic Cell Death as an Unprecedented Mode of Action Observed for New Bipyridine-Silver(I) Compounds Bearing Phosphane Coligands.Journal of medicinal chemistry · 2024Article
- The cross talk of ubiquitination and chemotherapy tolerance in colorectal cancer.Journal of cancer research and clinical oncology · 2024Review
- The cell-line-derived subcutaneous tumor model in preclinical cancer research.Nature protocols · 2022Review
- Targeting fibroblast growth factor receptors to combat aggressive ependymoma.Acta neuropathologica · 2021Article
- Article
- E3 Ubiquitin Ligase in Anticancer Drugdsla Resistance: Recent Advances and Future Potential.Frontiers in pharmacology · 2021Review
- p53 Loss Mediates Hypersensitivity to ETS Transcription Factor Inhibition Based on PARylation-Mediated Cell Death Induction.Cancers · 2020Article
- FGF9 promotes cisplatin resistance in colorectal cancer via regulation of Wnt/β-catenin signaling pathway.Experimental and therapeutic medicine · 2020Article
- CUL4A expression is associated with tumor stage and prognosis in nasopharyngeal carcinoma.Medicine · 2019Observational
- Cul4 E3 ubiquitin ligase regulates ovarian cancer drug resistance by targeting the antiapoptotic protein BIRC3.Cell death & disease · 2019Article
- The thiosemicarbazone MeCell death & disease · 2018Article
- Altered membrane rigidity via enhanced endogenous cholesterol synthesis drives cancer cell resistance to destruxins.Oncotarget · 2018Article
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundColorectal carcinoma (CRC) is the third most common cancer worldwide. Platinum-based anticancer compounds still constitute one mainstay of systemic CRC treatment despite limitations due to adverse effects and resistance development. Trabectedin has shown promising antitumor effects in CRC, however, again resistance development may occur. In this study, we aimed to develop strategies to circumvent or even exploit acquired trabectedin resistance in novel CRC treatment regimens.
methodsHuman HCT116 CRC cells were selected for acquired trabectedin resistance in vitro and characterised by cell biological as well as bioinformatic approaches. In vivo xenograft experiments were conducted.
resultsSelection of HCT116 cells for trabectedin resistance resulted in p53-independent hypersensitivity of the selected subline against cisplatin. Bioinformatic analyses of mRNA microarray data suggested deregulation of nucleotide excision repair and particularly loss of the ubiquitin ligase CUL4A in trabectedin-selected cells. Indeed, transient knockdown of CUL4A sensitised parental HCT116 cells towards cisplatin. Trabectedin selected but not parental HCT116 xenografts were significantly responsive towards cisplatin treatment.
conclusionsTrabectedin selection-mediated CUL4A loss generates an Achilles heel in CRC cancer cells enabling effective cisplatin treatment. Hence, inclusion of trabectedin in cisplatin-containing cancer treatment regimens might cause profound synergism based on reciprocal resistance prevention.
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