ArticleBreast cancer research : BCR2015
Preclinical evaluation of cyclin dependent kinase 11 and casein kinase 2 survival kinases as RNA interference targets for triple negative breast cancer therapy.
Article in Breast cancer research : BCR, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 70 citations in OpenAlex.
- Article
- CK2 in triple-negative breast cancer: oncogenic signaling networks and emerging CK2 inhibitor-based combination therapies.Clinical and experimental medicine · 2026Review
- Differential effects of oral contraceptives on lymph node metastasis in breast cancer: role of tumor size as an effect modifier.Journal of mammary gland biology and neoplasia · 2026Article
- Targeting CDK11 in Rhabdoid Tumor of the Kidney.Cancers · 2026Article
- In silico identification of bilobetin and ginsenoside as dual CK2 and ULK2 inhibitors targeting triple-negative breast cancer.Scientific reports · 2025Article
- CDK7-CDK11 axis in spliceosome regulation and pre-mRNA splicing.Nucleic acids research · 2025Article
- Mechanistic Roles of Transcriptional Cyclin-Dependent Kinases in Oncogenesis: Implications for Cancer Therapy.Cancers · 2025Review
- Cyclin-dependent protein kinases and cell cycle regulation in biology and disease.Signal transduction and targeted therapy · 2025Review
- Advances in siRNA Drug Delivery Strategies for Targeted TNBC Therapy.Bioengineering (Basel, Switzerland) · 2024Review
- Structural Characterization of Heat Shock Protein 90β and Molecular Interactions with Geldanamycin and Ritonavir: A Computational Study.International journal of molecular sciences · 2024Article
- CK2α-mediated phosphorylation of GRP94 facilitates the metastatic cascade in triple-negative breast cancer.Cell death discovery · 2024Article
- lncSNHG3 drives breast cancer progression by epigenetically increasing CSNK2A1 expression level.Aging · 2023Article
- Protein kinase CK2 - diverse roles in cancer cell biology and therapeutic promise.Molecular and cellular biochemistry · 2023Review
- Targeting pre-mRNA splicing in cancers: roles, inhibitors, and therapeutic opportunities.Frontiers in oncology · 2023Review
- Synthesis and Structure-Activity relationships of cyclin-dependent kinase 11 inhibitors based on a diaminothiazole scaffold.European journal of medicinal chemistry · 2022Article
- The Role of CDK Pathway Dysregulation and Its Therapeutic Potential in Soft Tissue Sarcoma.Cancers · 2022Review
- Identification of key tumor stroma-associated transcriptional signatures correlated with survival prognosis and tumor progression in breast cancer.Breast cancer (Tokyo, Japan) · 2022Article
- Targeting CK2 in cancer: a valuable strategy or a waste of time?Cell death discovery · 2021Review
- Genetic variations of DNA bindings of FOXA1 and co-factors in breast cancer susceptibility.Nature communications · 2021Article
- CX-4945 and siRNA-Mediated Knockdown of CK2 Improves Cisplatin Response in HPV(+) and HPV(-) HNSCC Cell Lines.Biomedicines · 2021Article
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
introductionTargeted therapies for aggressive breast cancers like triple negative breast cancer (TNBC) are needed. The use of small interfering RNAs (siRNAs) to disable expression of survival genes provides a tool for killing these cancer cells. Cyclin dependent kinase 11 (CDK11) is a survival protein kinase that regulates RNA transcription, splicing and mitosis. Casein kinase 2 (CK2) is a survival protein kinase that suppresses cancer cell death. Eliminating the expression of these genes has potential therapeutic utility for breast cancer.
methodsExpression levels of CDK11 and CK2 mRNAs and associated proteins were examined in breast cancer cell lines and tissue arrays. RNA expression levels of CDC2L1, CDC2L2, CCNL1, CCNL2, CSNK2A1, CSNK2A2, and CSNK2B genes in breast cancer subtypes were analyzed. Effects following transfection of siRNAs against CDK11 and CK2 in cultured cells were examined by viability and clonal survival assays and by RNA and protein measures. Uptake of tenfibgen (TBG) nanocapsules by TNBC cells was analyzed by fluorescence-activated cell sorting. TBG nanocapsules delivered siRNAs targeting CDK11 or CK2 in mice carrying TNBC xenograft tumors. Transcript cleavage and response parameters were evaluated.
resultsWe found strong CDK11 and CK2 mRNA and protein expression in most human breast cancer cells. Immunohistochemical analysis of TNBC patient tissues showed 100% of tumors stained positive for CDK11 with high nuclear intensity compared to normal tissue. The Cancer Genome Atlas analysis comparing basal to other breast cancer subtypes and to normal breast revealed statistically significant differences. Down-regulation of CDK11 and/or CK2 in breast cancer cells caused significant loss of cell viability and clonal survival, reduced relevant mRNA and protein expression, and induced cell death changes. TBG nanocapsules were taken up by TNBC cells both in culture and in xenograft tumors. Treatment with TBG- siRNA to CDK11 or TBG- siRNA to CK2αα' nanocapsules induced appropriate cleavage of CDK11 and CK2α transcripts in TNBC tumors, and caused MDA-MB-231 tumor reduction, loss of proliferation, and decreased expression of targeted genes.
conclusionsCDK11 and CK2 expression are individually essential for breast cancer cell survival, including TNBC. These genes serve as promising new targets for therapeutic development in breast cancer.
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