ArticleCancers2021
The Small-Molecule Inhibitor MRIA9 Reveals Novel Insights into the Cell Cycle Roles of SIK2 in Ovarian Cancer Cells.
Article in Cancers, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 21 citations in OpenAlex.
- Mechanisms of Paclitaxel Resistance: Recent Advances and Future Perspectives.International journal of molecular sciences · 2026Review
- A Review of SIK2 in Ovarian Cancer: Function and Emerging Targeted Therapies.OncoTargets and therapy · 2026Review
- High-Quality In Vivo Chemical Probes for Protein Kinases Disclosed in 2024.ACS pharmacology & translational science · 2025Review
- Sex difference in human diseases: mechanistic insights and clinical implications.Signal transduction and targeted therapy · 2024Review
- Identification of highly selective SIK1/2 inhibitors that modulate innate immune activation and suppress intestinal inflammation.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Roles of salt‑inducible kinases in cancer (Review).International journal of oncology · 2023Review
- Inhibiting eukaryotic initiation factor 5A (eIF5A) hypusination attenuated activation of the SIK2 (salt-inducible kinase 2)-p4E-BP1 pathway involved in ovarian cancer cell proliferation and migration.Molecular biology reports · 2023Article
- The multiple roles of salt-inducible kinases in regulating physiology.Physiological reviews · 2023Review
- Ubiquitination and degradation of SIK2 by DNA-PKcs deficiency promote radiation-induced mitotic catastrophe.Genes & diseases · 2023Article
- Structure-based design of selective, orally available salt-inducible kinase inhibitors that stimulate bone formation in mice.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- The non-apoptotic function of Caspase-8 in negatively regulating the CDK9-mediated Ser2 phosphorylation of RNA polymerase II in cervical cancer.Cellular and molecular life sciences : CMLS · 2022Article
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
The activity of the Salt inducible kinase 2 (SIK2), a member of the AMP-activated protein kinase (AMPK)-related kinase family, has been linked to several biological processes that maintain cellular and energetic homeostasis. SIK2 is overexpressed in several cancers, including ovarian cancer, where it promotes the proliferation of metastases. Furthermore, as a centrosome kinase, SIK2 has been shown to regulate the G2/M transition, and its depletion sensitizes ovarian cancer to paclitaxel-based chemotherapy. Here, we report the consequences of SIK2 inhibition on mitosis and synergies with paclitaxel in ovarian cancer using a novel and selective inhibitor, MRIA9. We show that MRIA9-induced inhibition of SIK2 blocks the centrosome disjunction, impairs the centrosome alignment, and causes spindle mispositioning during mitosis. Furthermore, the inhibition of SIK2 using MRIA9 increases chromosomal instability, revealing the role of SIK2 in maintaining genomic stability. Finally, MRIA9 treatment enhances the sensitivity to paclitaxel in 3D-spheroids derived from ovarian cancer cell lines and ovarian cancer patients. Our study suggests selective targeting of SIK2 in ovarian cancer as a therapeutic strategy for overcoming paclitaxel resistance.
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Registered trials
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.