ArticleCell death & disease2022
Midkine noncanonically suppresses AMPK activation through disrupting the LKB1-STRAD-Mo25 complex.
Article in Cell death & disease, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed.
- Low Serum LDL-C Is Associated with Poorer Overall Survival and Lipid-Related Molecular Features in Colorectal Cancer.Biomedicines · 2026Article
- MDK Activates the PI3K/AKT Axis to Induce AP2A1 Expression and Epithelial-Mesenchymal Transition in Colorectal Cancer.Cancers · 2026Article
- Midkine (MDK) as a central regulator of the tumor microenvironment: From developmental cytokine to therapeutic target.Cancer letters · 2026Review
- Senescent epithelial cells remodel the tumor microenvironment and drive early LUAD progression: a multiomics risk model and single-cell analysis.Cellular and molecular life sciences : CMLS · 2026Article
- Significance of Midkine Signaling in Women's Cancers: Novel Biomarker and Therapeutic Target.International journal of molecular sciences · 2025Review
- Protein phosphatase 1 regulatory subunit 15 A (PPP1R15A) promoted the progression of gastric cancer by activating cell autophagy under energy stress.Journal of experimental & clinical cancer research : CR · 2025Article
- Multi-omics reveals the mechanism of Trimethylamine N-oxide derived from gut microbiota inducing liver fatty of dairy cows.BMC genomics · 2025Article
- eQTL and multi-omics integration reveal PPIH as a prognostic and immunotherapeutic biomarker.Frontiers in immunology · 2025Article
- A novel effect of bevacizumab in reducing characteristic pigmentation in Peutz-Jeghers syndrome: a case report and literature review.Frontiers in oncology · 2025Article
- Spatiotemporal Molecular Architecture of Lineage Allocation and Cellular Organization in Tooth Morphogenesis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- GPC2 promotes prostate cancer progression via MDK-mediated activation of PI3K/AKT signaling pathway.Functional & integrative genomics · 2024Article
- Midkine: A Cancer Biomarker Candidate and Innovative Therapeutic Approaches.European journal of breast health · 2024Article
- Nasopharynx Battlefield: Cellular Immune Responses Mediated by Midkine in Nasopharyngeal Carcinoma and COVID-19.Cancers · 2023Review
- 6-Gingerol Ameliorates Hepatic Steatosis, Inflammation and Oxidative Stress in High-Fat Diet-Fed Mice through Activating LKB1/AMPK Signaling.International journal of molecular sciences · 2023Article
- Multi-omics analysis reveals cuproptosis and mitochondria-based signature for assessing prognosis and immune landscape in osteosarcoma.Frontiers in immunology · 2023Article
- The crosstalk among the physical tumor microenvironment and the effects of glucose deprivation on tumors in the past decade.Frontiers in cell and developmental biology · 2023Review
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Authors and funding
12 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Midkine (MDK), a secreted growth factor, regulates signal transduction and cancer progression by interacting with receptors, and it can be internalized into the cytoplasm by endocytosis. However, its intracellular function and signaling regulation remain unclear. Here, we show that intracellular MDK interacts with LKB1 and STRAD to disrupt the LKB1-STRAD-Mo25 complex. Consequently, MDK decreases the activity of LKB1 to dampen both the basal and stress-induced activation of AMPK by glucose starvation or treatment of 2-DG. We also found that MDK accelerates cancer cell proliferation by inhibiting the activation of the LKB1-AMPK axis. In human cancers, compared to other well-known growth factors, MDK expression is most significantly upregulated in cancers, especially in liver, kidney and breast cancers, correlating with clinical outcomes and inversely correlating with phosphorylated AMPK levels. Our study elucidates an inhibitory mechanism for AMPK activation, which is mediated by the intracellular MDK through disrupting the LKB1-STRAD-Mo25 complex.
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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 Socratic graph.