ArticleOncogene2021
Vaccinia-related kinase 2 blunts sorafenib's efficacy against hepatocellular carcinoma by disturbing the apoptosis-autophagy balance.
Article in Oncogene, 2021. 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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Who cites it
17 citing papers in PubMed, 16 citations in OpenAlex.
- VRK3 promotes KSHV infection by suppressing the antiviral type I interferon response.PLoS pathogens · 2026Article
- Silencing of SIVA‑1 promotes cisplatin resistance in gastric cancer via the Bcl‑2/BAX‑mediated mitochondria‑dependent apoptosis pathway.Oncology reports · 2026Article
- The ATG14: multi-layer autophagy control and an emerging therapeutic target in cancer.Apoptosis : an international journal on programmed cell death · 2026Review
- Vaccinia-related kinase 2 inhibition elicits vulnerability of glutathione metabolism in pancreatic cancer.Cell death & disease · 2026Article
- Mechanistic Research on the Crosstalk Between Macrophage Polarization and Energy Metabolic Reprogramming in Hepatocellular Carcinoma.Journal of hepatocellular carcinoma · 2026Review
- Mitochondria-related genes or proteins affect the progression of hepatocellular carcinoma: roles, mechanisms and potential treatments.American journal of cancer research · 2026Review
- DNA methylation and bronchiectasis: a Mendelian randomization analysis to investigate causal link and therapeutic target.Epigenetics · 2025Article
- VRK2 targeting potentiates anti-PD-1 immunotherapy in hepatocellular carcinoma through MYC destabilization.Nature communications · 2025Article
- Patient-derived xenograft model: Applications and challenges in liver cancer.Chinese medical journal · 2025Review
- Integrating bioinformatics and experimental validation to reveal a novel VRK score as a prognostic and therapeutic biomarker in hepatocellular carcinoma.Frontiers in immunology · 2025Article
- SLC35F2-SYVN1-TRIM59 axis critically regulates ferroptosis of pancreatic cancer cells by inhibiting endogenous p53.Oncogene · 2023Article
- Elevated FBXL6 expression in hepatocytes activates VRK2-transketolase-ROS-mTOR-mediated immune evasion and liver cancer metastasis in mice.Experimental & molecular medicine · 2023Article
- Pathogenesis of Hepatocellular Carcinoma: The Interplay of Apoptosis and Autophagy.Biomedicines · 2023Review
- Targeting and regulation of autophagy in hepatocellular carcinoma: revisiting the molecular interactions and mechanisms for new therapy approaches.Cell communication and signaling : CCS · 2023Review
- Drug resistance mechanism of kinase inhibitors in the treatment of hepatocellular carcinoma.Frontiers in pharmacology · 2023Review
- miR-15a and miR-20b sensitize hepatocellular carcinoma cells to sorafenib through repressing CDC37L1 and consequent PPIA downregulation.Cell death discovery · 2022Article
- MicroRNA-138-1-3p sensitizes sorafenib to hepatocellular carcinoma by targeting PAK5 mediated β-catenin/ABCB1 signaling pathway.Journal of biomedical science · 2021Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hepatocellular carcinoma (HCC) is a lethal malignancy with limited treatment options. Sorafenib is the only Food and Drug Administration (FDA)-approved first-line targeted drug for the treatment of advanced HCC. However, its effect on patient survival is limited. Recently, studies have demonstrated that the imbalance between apoptosis and autophagy plays a critical role in chemoresistance, and it is hypothesised that restoring the balance between these processes is a potential treatment strategy for improving chemoresistance in cancer. However, there is currently no evidence supporting this hypothesis. We aimed to investigate if vaccinia-related kinase 2 (VRK2), a serine/threonine protein kinase, confers sorafenib resistance in HCC cells. Here, we found that VRK2 was enriched in sorafenib-resistant HCC cells and patient-derived xenografts. Both in vivo and in vitro evidences showed that VRK2 blunts the efficacy of sorafenib against hepatocellular carcinoma by disturbing the balance between apoptosis and autophagy. Mechanistically, VRK2 promotes the phosphorylation of Bcl-2 by activating JNK1/MAPK8, thereby enhancing the dissociation of Bcl-2 from Beclin-1 and promoting the formation of the Beclin-1-Atg14-Vps34 complex, which facilitates autophagy. Furthermore, VRK2-induced phosphorylation of Bcl-2 promotes the interaction of Bcl-2 with BAX, thereby inhibiting apoptosis. In conclusion, targeting VRK2 for modulation of the balance between autophagy and apoptosis may be a novel strategy for overcoming sorafenib resistance in HCC.
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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 Socratic graph.