ArticleCell death & disease2019
CK2 inhibition with silmitasertib promotes methuosis-like cell death associated to catastrophic massive vacuolization of colorectal cancer cells.
Article in Cell death & disease, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.
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Who cites it
36 citing papers in PubMed, 1 synthesis or guideline pooled it, 62 citations in OpenAlex.
- CSNK2 in cancer: pathophysiology and translational applications.British journal of cancer · 2022Pooled it
- CK2 in triple-negative breast cancer: oncogenic signaling networks and emerging CK2 inhibitor-based combination therapies.Clinical and experimental medicine · 2026Review
- Review
- Silmitasertib, an FDA-designated orphan CK2 inhibitor, ameliorates neuropathology and motor dysfunction in a Huntington's disease mouse model.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- Silmitasertib, an FDA-designated orphan CK2 Inhibitor, ameliorates neuropathology and motor dysfunction in a Huntington's disease mouse model.bioRxiv : the preprint server for biology · 2025Article
- Macropinocytosis: Both a Target and a Tool for Cancer Therapy.Biomolecules · 2025Review
- Ellagic Acid Mediates the Delay of Dermal Fibroblast Senescence via CSNK2A1.Clinical, cosmetic and investigational dermatology · 2025Article
- Cisplatin-resistance and aggressiveness are enhanced by a highly stable endothelin-converting enzyme-1c in lung cancer cells.Biological research · 2024Article
- Novel selective inhibitors of macropinocytosis-dependent growth in pancreatic ductal carcinoma.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2024Article
- Cellular Regulation of Macropinocytosis.International journal of molecular sciences · 2024Review
- Casein kinase 2 phosphorylates and induces the SALL2 tumor suppressor degradation in colon cancer cells.Cell death & disease · 2024Article
- Scoping Pleiotropy of CK2 in Musculoskeletal Disorders for a Novel Targeting Approach.Kinases and phosphatases · 2024Article
- Mechanism study of oleanolic acid derivative, K73-03, inducing cell apoptosis in hepatocellular carcinoma.Cancer cell international · 2024Article
- Tanshinlactone triggers methuosis in breast cancer cells via NRF2 activation.Frontiers in pharmacology · 2024Article
- Tubeimoside-2 Triggers Methuosis in Hepatocarcinoma Cells through the MKK4-p38α Axis.Pharmaceutics · 2023Article
- CircNDST1 promotes papillary thyroid cancer progression via its interaction with CSNK2A1 to activate the PI3K-Akt pathway and epithelial-mesenchymal transition.Journal of endocrinological investigation · 2023Article
- Article
- Inhibition of Macropinocytosis Enhances the Sensitivity of Osteosarcoma Cells to Benzethonium Chloride.Cancers · 2023Article
- CK2 and the Hallmarks of Cancer.Biomedicines · 2022Review
- Methuosis Contributes to Jaspine-B-Induced Cell Death.International journal of molecular sciences · 2022Article
Corrections and comments
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Authors and funding
13 authors at 7 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Protein kinase CK2 is a highly conserved and constitutively active Ser/Thr-kinase that phosphorylates a large number of substrates, resulting in increased cell proliferation and survival. A known target of CK2 is Akt, a player in the PI3K/Akt/mTORC1 signaling pathway, which is aberrantly activated in 32% of colorectal cancer (CRC) patients. On the other hand, mTORC1 plays an important role in the regulation of protein synthesis, cell growth, and autophagy. Some studies suggest that CK2 regulates mTORC1 in several cancers. The most recently developed CK2 inhibitor, silmitasertib (formerly CX-4945), has been tested in phase I/II trials for cholangiocarcinoma and multiple myeloma. This drug has been shown to induce autophagy and enhance apoptosis in pancreatic cancer cells and to promote apoptosis in non-small cell lung cancer cells. Nevertheless, it has not been tested in studies for CRC patients. We show in this work that inhibition of CK2 with silmitasertib decreases in vitro tumorigenesis of CRC cells in response to G2/M arrest, which correlates with mTORC1 inhibition and formation of large cytoplasmic vacuoles. Notably, molecular markers indicate that these vacuoles derive from massive macropinocytosis. Altogether, these findings suggest that an aberrantly elevated expression/activity of CK2 may play a key role in CRC, promoting cell viability and proliferation in untreated cells, however, its inhibition with silmitasertib promotes methuosis-like cell death associated to massive catastrophic vacuolization, accounting for decreased tumorigenicity at later times. These characteristics of silmitasertib support a potential therapeutic use in CRC patients and probably other CK2-dependent cancers.
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