ArticlePloS one2018
Autophagic cell death associated to Sorafenib in renal cell carcinoma is mediated through Akt inhibition in an ERK1/2 independent fashion.
Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 28 citations in OpenAlex.
- Elevated neuregulin‑1 expression modulates tumor malignancy and autophagy in esophageal squamous cell carcinoma.International journal of molecular medicine · 2025Article
- MAPK11 (p38β) is a major determinant of cellular radiosensitivity by controlling ionizing radiation-associated senescence: An in vitro study.Clinical and translational radiation oncology · 2023Article
- Autophagy: A challengeable paradox in cancer treatment.Cancer medicine · 2023Review
- KRIT1: A Traffic Warden at the Busy Crossroads Between Redox Signaling and the Pathogenesis of Cerebral Cavernous Malformation Disease.Antioxidants & redox signaling · 2023Review
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- Understanding the Role of Autophagy in Cancer Formation and Progression Is a Real Opportunity to Treat and Cure Human Cancers.Cancers · 2021Review
- ERK5 signalling pathway is a novel target of sorafenib: Implication in EGF biology.Journal of cellular and molecular medicine · 2021Article
- Kidney cancer biomarkers and targets for therapeutics: survivin (BIRC5), XIAP, MCL-1, HIF1α, HIF2α, NRF2, MDM2, MDM4, p53, KRAS and AKT in renal cell carcinoma.Journal of experimental & clinical cancer research : CR · 2021Review
- Hydroxychloroquine Potentiates Apoptosis Induced by PPARPPAR research · 2021Article
- Development of an Autophagy-Related Gene Prognostic Model and Nomogram for Estimating Renal Clear Cell Carcinoma Survival.Journal of oncology · 2021Article
- Suppressive effects of RASAL2 on renal cell carcinoma via SOX2/ERK/p38 MAPK pathway.Experimental and therapeutic medicine · 2020Article
- Review
- Synthesis, in vitro, and in vivo evaluation of novel N-phenylindazolyl diarylureas as potential anti-cancer agents.Scientific reports · 2020Article
- SETD2 mutation in renal clear cell carcinoma suppress autophagy via regulation of ATG12.Cell death & disease · 2020Article
- Exosomes derived from cardiac parasympathetic ganglionic neurons inhibit apoptosis in hyperglycemic cardiomyoblasts.Molecular and cellular biochemistry · 2019Article
- CDK5: Key Regulator of Apoptosis and Cell Survival.Biomedicines · 2019Review
- Cell death-related molecules and biomarkers for renal cell carcinoma targeted therapy.Cancer cell international · 2019Review
- CDK5RAP3 Participates in Autophagy Regulation and Is Downregulated in Renal Cancer.Disease markers · 2019Article
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectivesTo fully clarify the role of Mitogen Activated Protein Kinase in the therapeutic response to Sorafenib in Renal Cell Carcinoma as well as the cell death mechanism associated to this kinase inhibitor, we have evaluated the implication of several Mitogen Activated Protein Kinases in Renal Cell Carcinoma-derived cell lines. MATERIALS AND
methodsAn experimental model of Renal Cell Carcinoma-derived cell lines (ACHN and 786-O cells) was evaluated in terms of viability by MTT assay, induction of apoptosis by caspase 3/7 activity, autophagy induction by LC3 lipidation, and p62 degradation and kinase activity using phospho-targeted antibodies. Knock down of ATG5 and ERK5 was performed using lentiviral vector coding specific shRNA.
resultsOur data discard Extracellular Regulated Kinase 1/2 and 5 as well as p38 Mitogen Activated Protein Kinase pathways as mediators of Sorafenib toxic effect but instead indicate that the inhibitory effect is exerted through the PI3K/Akt signalling pathway. Furthermore, we demonstrate that inhibition of Akt mediates cell death associated to Sorafenib without caspase activation, and this is consistent with the induction of autophagy, as indicated by the use of pharmacological and genetic approaches.
conclusionThe present report demonstrates that Sorafenib exerts its toxic effect through the induction of autophagy in an Akt-dependent fashion without the implication of Mitogen Activated Protein Kinase. Therefore, our data discard the use of inhibitors of the RAF-MEK-ERK1/2 signalling pathway in RCC and support the use of pro-autophagic compounds, opening new therapeutic opportunities for Renal Cell Carcinoma.
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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.