ArticleOncogene2022
SIK2 maintains breast cancer stemness by phosphorylating LRP6 and activating Wnt/β-catenin signaling.
Article in Oncogene, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 24 citations in OpenAlex.
- Study of Estrogen Receptor-Mediated PGx-eQTLs Identifies Genetic Determinants of Breast Cancer Endocrine Therapy Response.International journal of molecular sciences · 2026Article
- SIK inhibitor HG-9-91-01 suppresses the pathogenic activity of fibroblast-like synoviocytes in rheumatoid arthritis.RMD open · 2026Article
- Translational insights and clinical challenges of targeting cancer stem cells.Signal transduction and targeted therapy · 2026Review
- Decoding the Oncogenic Role of GNG10 in Colorectal Cancer: A Non-Canonical Wnt Pathway-Driven Mechanism.Journal of cellular and molecular medicine · 2026Article
- Is cancer the result of uncontrolled cellular growth? a glance into the tumorigenic process.Cancer cell international · 2026Review
- ZNF33A activates Wnt/β-catenin signaling and promotes BCAA catabolism in colorectal cancer.Cell communication and signaling : CCS · 2026Article
- WNT signaling in cancer: molecular mechanisms and potential therapies.Molecular biomedicine · 2025Review
- Role of the Wnt signaling pathway in the complex microenvironment of breast cancer and prospects for therapeutic potential (Review).International journal of oncology · 2025Review
- Salt-inducible kinase 2 confers radioresistance in colorectal cancer by facilitating homologous recombination repair.MedComm · 2025Article
- LRP11 facilitates lipid metabolism and malignancy in hepatocellular carcinoma by stabilizing RACK1 through USP5 regulation.Molecular medicine (Cambridge, Mass.) · 2025Article
- SIK2 inhibitor SIC-19 enhances the sensitivity of PARP inhibitors in triple-negative breast cancers and pancreatic cancers.Oncology research · 2025Article
- Exosomal miR-502-5p suppresses the progression of gastric cancer by repressing angiogenesis through the Wnt/β-catenin pathway.Irish journal of medical science · 2024Article
- Review
- The inhibition of YTHDF3/mInternational journal of biological sciences · 2024Article
- Function and prognosis analysis of nucleolus protein DCAF13 in breast cancer.Translational cancer research · 2023Article
- Breast cancer stem cells generate immune-suppressive T regulatory cells by secreting TGFβ to evade immune-elimination.Discover oncology · 2023Article
- Roles of salt‑inducible kinases in cancer (Review).International journal of oncology · 2023Review
- Regulation and signaling pathways in cancer stem cells: implications for targeted therapy for cancer.Molecular cancer · 2023Review
- The AMPK-like protein kinases Sik2 and Sik3 interact with Hipk and induce synergistic tumorigenesis in aFrontiers in cell and developmental biology · 2023Article
- Signaling pathways governing the maintenance of breast cancer stem cells and their therapeutic implications.Frontiers in cell and developmental biology · 2023Review
Corrections and comments
- Erratum issued
Authors and funding
25 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Breast cancer stem cells (BCSCs) are the main drivers of recurrence and metastasis. However, commonly used drugs rarely target BCSCs. Via screenings, we found that Salt-inducible kinase 2 (SIK2) participated in breast cancer (BC) stemness maintenance and zebrafish embryos development. SIK2 was upregulated in recurrence samples. Knockdown of SIK2 expression reduced the proportion of BCSCs and the tumor initiation of BC cells. Mechanistically, SIK2, phosphorylated by CK1α, directly phosphorylated LRP6 in a SIK2 kinase activity-dependent manner, leading to Wnt/β-catenin signaling pathway activation. ARN-3236 and HG-9-91-01, inhibitors of SIK2, inhibited LRP6 phosphorylation and β-catenin accumulation and disturbed stemness maintenance. In addition, the SIK2-activated Wnt/β-catenin signaling led to induction of IDH1 expression, causing metabolic reprogramming in BC cells. These findings demonstrate a novel mechanism whereby Wnt/β-catenin signaling pathway is regulated by different kinases in response to metabolic requirement of CSCs, and suggest that SIK2 inhibition may potentially be a strategy for eliminating BCSCs.
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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.