ArticleNeoplasia (New York, N.Y.)2019
Mitochondrial Function of CKS2 Oncoprotein Links Oxidative Phosphorylation with Cell Division in Chemoradioresistant Cervical Cancer.
Article in Neoplasia (New York, N.Y.), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 30 citations in OpenAlex.
- Pathogenic Mechanisms in Cervical Cancer: Energy Metabolism, Hypoxia and Therapy.Life (Basel, Switzerland) · 2026Review
- TSPOAP1-AS1: A Novel Biomarker for the Prognosis and Therapeutic Target in Cervical Cancer.Combinatorial chemistry & high throughput screening · 2026Article
- Proximity Ligation Assay: From a Foundational Principle to a Versatile Platform for Molecular and Translational Research.Biomolecules · 2025Review
- Facilitation of natural killer T-cell cytotoxic activity in uterine sarcoma via theTranslational cancer research · 2025Article
- CKS2 Mediates Hepatocellular Carcinoma Recurrence After Hepatic Ischemia-Reperfusion Injury Related to M2 Macrophages.Journal of inflammation research · 2025Article
- Unveiling CKS2: A Key Player in Aggressive B-Cell Lymphoma Progression and a Target for Synergistic Therapy.Cancer medicine · 2024Article
- A gene signature linked to fibroblast differentiation for prognostic prediction of mesothelioma.Cell & bioscience · 2024Article
- Biological functions and therapeutic potential of CKS2 in human cancer.Frontiers in oncology · 2024Review
- ZNF695, A Potential Prognostic Biomarker, Correlates with Im mune Infiltrates in Cervical Squamous Cell Carcinoma and Endoce rvical Adenocarcinoma: Bioinformatic Analysis and Experimental Verification.Current gene therapy · 2024Article
- Pareto task inference analysis reveals cellular trade-offs in diffuse large B-Cell lymphoma transcriptomic data.Frontiers in systems biology · 2024Article
- Identification ofTranslational cancer research · 2023Article
- Cyclin-dependent kinase subunit2 (CKS2) promotes malignant phenotypes and epithelial-mesenchymal transition-like process in glioma by activating TGFβ/SMAD signaling.Cancer medicine · 2023Article
- Comprehensive analysis of the progression mechanisms of CRPC and its inhibitor discovery based on machine learning algorithms.Frontiers in genetics · 2023Article
- Overexpression of Parkin in clear cell renal cell carcinoma decreases tumor aggressiveness by regulating CKS2 levels.International journal of oncology · 2022Article
- Identification of therapeutically potential targets and their ligands for the treatment of OSCC.Frontiers in oncology · 2022Article
- Identification of aberrantly methylated differentially expressed genes and pro-tumorigenic role of KIF2C in melanoma.Frontiers in genetics · 2022Article
- Comprehensive Expression Profiling and Molecular Basis of CDC28 Protein Kinase Regulatory Subunit 2 in Cervical Cancer.International journal of genomics · 2022Article
- Predicting brain metastasis in early stage non-small cell lung cancer patients by gene expression profiling.Translational lung cancer research · 2020Article
- Cyclin-Dependent Kinase Regulatory Subunit 2 Indicated Poor Prognosis and Facilitated Aggressive Phenotype of Hepatocellular Carcinoma.Disease markers · 2019Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
CDK regulatory subunit 2 (CKS2) has a nuclear function that promotes cell division and is a candidate biomarker of chemoradioresistance in cervical cancer. The underlying mechanisms are, however, not completely understood. We investigated whether CKS2 also has a mitochondrial function that augments tumor aggressiveness. Based on global gene expression data of two cervical cancer cohorts of 150 and 135 patients, we identified a set of genes correlated with CKS2 expression. Gene set enrichment analysis showed enrichment of mitochondrial cellular compartments, and the hallmarks oxidative phosphorylation (OXPHOS) and targets of the MYC oncogene in the gene set. By in situ proximity ligation assay, we showed that CKS2 formed complex with the positively correlated MYC target, mitochondrial single-stranded DNA binding protein SSBP1, in the mitochondrion of cervix tumor samples and HeLa and SiHa cervical cancer cell lines, indicating a role in mitochondrial DNA (mtDNA) replication and thereby OXPHOS. CDK1 was found to be part of the complex. Flow cytometry analyses of HeLa cells showed cell cycle regulation of the CKS2-SSBP1 complex consistent with mtDNA replication activity. Moreover, repression of mtDNA replication and OXPHOS by acute hypoxia decreased CKS2-SSBP1 complex abundance and expression of MYC targets. By immunohistochemistry, cytoplasmic CKS2 expression was found to add to the prognostic impact of nuclear CKS2 expression in patients, suggesting that the mitochondrial function promotes tumor aggressiveness. Our study uncovers a novel link between regulation of cell division by nuclear pathways and OXPHOS in the mitochondrion that involves CKS2 and promotes chemoradioresistance of cervical cancer.
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