ArticleCell death discovery2019
Prosurvival autophagy is regulated by protein kinase CK1 alpha in multiple myeloma.
Article in Cell death discovery, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 26 citations in OpenAlex.
- Novel therapeutic targets at the crossroad between epigenetics and signal transduction pathways in B-cell lymphomas.Clinical and experimental medicine · 2026Review
- Forcing Ahead: Second-Line Treatment Options for Lenalidomide-Refractory Multiple Myeloma.Cancers · 2025Review
- Wnt/β-catenin signaling pathway: proteins' roles in osteoporosis and cancer diseases and the regulatory effects of natural compounds on osteoporosis.Molecular medicine (Cambridge, Mass.) · 2024Review
- Multisystem disorder associated with a pathogenic variant in CLCN7 in the absence of osteopetrosis.Molecular genetics & genomic medicine · 2024Article
- Oocyte Casein kinase 1α deletion causes defects in primordial follicle formation and oocyte loss by impairing oocyte meiosis and enhancing autophagy in developing mouse ovary.Cell death discovery · 2022Article
- CRL4Cancers · 2022Review
- CK1α/RUNX2 Axis in the Bone Marrow Microenvironment: A Novel Therapeutic Target in Multiple Myeloma.Cancers · 2022Article
- Molecular Mechanisms of Cereblon-Interacting Small Molecules in Multiple Myeloma Therapy.Journal of personalized medicine · 2021Review
- Casein Kinase-1-Alpha Inhibitor (D4476) Sensitizes Microsatellite Instable Colorectal Cancer Cells to 5-Fluorouracil via Authophagy Flux Inhibition.Archivum immunologiae et therapiae experimentalis · 2021Article
- Stress-activated kinases as therapeutic targets in pancreatic cancer.World journal of gastroenterology · 2021Review
- Targeting Protein Kinases in Blood Cancer: Focusing on CK1α and CK2.International journal of molecular sciences · 2021Review
- Protein Kinase CK1α Sustains B-Cell Receptor Signaling in Mantle Cell Lymphoma.Frontiers in oncology · 2021Article
- Article
- Targeting Casein Kinase 1 (CK1) in Hematological Cancers.International journal of molecular sciences · 2020Review
- Casein kinase 1α inhibits p53 downstream of MDM2‑mediated autophagy and apoptosis in acute myeloid leukemia.Oncology reports · 2020Article
- Prediction of cancer driver genes through network-based moment propagation of mutation scores.Bioinformatics (Oxford, England) · 2020Article
- Actionable Strategies to Target Multiple Myeloma Plasma Cell Resistance/Resilience to Stress: Insights From "Omics" Research.Frontiers in oncology · 2020Review
- Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Multiple myeloma (MM) is a tumor of plasma cells (PCs). Due to the intense immunoglobulin secretion, PCs are prone to endoplasmic reticulum stress and activate several stress-managing pathways, including autophagy. Indeed, autophagy deregulation is maladaptive for MM cells, resulting in cell death. CK1α, a pro-survival kinase in MM, has recently been involved as a regulator of the autophagic flux and of the transcriptional competence of the autophagy-related transcription factor FOXO3a in several cancers. In this study, we investigated the role of CK1α in autophagy in MM. To study the autophagic flux we generated clones of MM cell lines expressing the mCherry-eGFP-LC3B fusion protein. We observed that CK1 inhibition with the chemical ATP-competitive CK1 α/δ inhibitor D4476 resulted in an impaired autophagic flux, likely due to an alteration of lysosomes acidification. However, D4476 caused the accumulation of the transcription factor FOXO3a in the nucleus, and this was paralleled by the upregulation of mRNA coding for autophagic genes. Surprisingly, silencing of CK1α by RNA interference triggered the autophagic flux. However, FOXO3a did not shuttle into the nucleus and the transcription of autophagy-related FOXO3a-dependent genes was not observed. Thus, while the chemical inhibition with the dual CK1α/δ inhibitor D4476 induced cell death as a consequence of an accumulation of ineffective autophagic vesicles, on the opposite, CK1α silencing, although it also determined apoptosis, triggered a full activation of the early autophagic flux, which was then not supported by the upregulation of autophagic genes. Taken together, our results indicate that the family of CK1 kinases may profoundly influence MM cells survival also through the modulation of the autophagic pathway.
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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.