ArticleScientific reports2025
BRSK2 plays a role in autophagy and cancer cell growth and survival under nutrient deprivation stress via the PIK3C3 pathway.
Article in Scientific reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Article
- BRSK2 accumulation mediated by TRIM28 accelerates hepatocellular carcinoma progression via activating the PI3K/AKT/mTOR signaling pathway.Molecular and cellular biochemistry · 2026Article
- p62/SQSTM1-TRAF6/RIP1 complexes activate NF-κB-mediated PD-L1 expression and promote T-cell apoptosis in MKN45 gastric cancer cells.Journal of gastrointestinal oncology · 2026Article
- The Crosstalk Between Epithelial-Mesenchymal Transition and Anoikis Resistance: A New Perspective of Traditional Chinese Medicine to Prevent Tumor Metastasis.Drug design, development and therapy · 2026Review
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Authors and funding
12 authors.
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Abstract
Macroautophagy/autophagy is a stress-responsive lysosomal catabolic pathway that promotes cellular homeostasis and tumor cell survival, but its role in breast cancer progression and metastasis remains unclear. Here, we show that a brain-specific serine/threonine protein kinase, BRSK2, a marker of aggressive metastatic disease in breast cancer patients, is crucial in regulating autophagy. BRSK2 is overexpressed in aggressive cancer and is associated with reduced disease-specific survival. BRSK2 also regulates basal autophagy and activates AKT, STAT3, and NF-κB-mediated cancer cell survival pathways. In addition, BRSK2 overexpression increases the levels of inflammatory cytokines and chemokines in breast cancer cells. Downregulation of BRSK2 using specific siRNAs or the BRSK2 kinase small-molecule inhibitor GW296115 markedly reduced nutrient-deprivation stress-mediated autophagy, cell growth, and metastatic potential, and enhanced breast cancer cell apoptosis. Endogenous BRSK2 is associated with the Vps34-class III PI3K-Beclin-1-ATG14 autophagy signaling complexes that could protect cancer cells from nutrient-deprivation stress. Our findings demonstrate the key role of the BRSK2-mediated protective autophagy and cell growth and survival under nutrient deprivation stress via survival signals, e.g., PI3K/AKT or STAT3-NF-kB, in aggressive breast cancer cells.
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