ArticleOncotarget2017
Midkine promotes hepatocellular carcinoma metastasis by elevating anoikis resistance of circulating tumor cells.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 57 citations in OpenAlex.
- Nanoparticle-based strategies targeting disulfidptosis, anoikis, and PANoptosis for enhanced cancer therapy.Journal of nanobiotechnology · 2026Review
- Rewiring immunity: Midkine's emerging role in cancer immune escape and drug resistance.iScience · 2026Review
- Retraction: HMGB2 upregulation promotes the progression of hepatocellular carcinoma cells through the activation of ZEB1/vimentin axis.Journal of gastrointestinal oncology · 2026Article
- Midkine (MDK) in cancer and drug resistance: from inflammation to therapy.Discover oncology · 2025Review
- New insights into biomarkers and risk stratification to predict hepatocellular cancer.Molecular medicine (Cambridge, Mass.) · 2025Review
- Roles of anoikis in hepatocellular carcinoma: mechanisms and therapeutic potential.Medical oncology (Northwood, London, England) · 2025Review
- Survival mechanisms of circulating tumor cells and their implications for cancer treatment.Cancer metastasis reviews · 2024Review
- tRNA-derived fragment 3'tRF-AlaAGC modulates cell chemoresistance and M2 macrophage polarization via binding to TRADD in breast cancer.Journal of translational medicine · 2024Article
- Midkine: A Cancer Biomarker Candidate and Innovative Therapeutic Approaches.European journal of breast health · 2024Article
- Review
- Qizhu Anti-Cancer Recipe promotes anoikis of hepatocellular carcinoma cells by activating the c-Jun N-terminal kinase pathway.Heliyon · 2023Article
- Nasopharynx Battlefield: Cellular Immune Responses Mediated by Midkine in Nasopharyngeal Carcinoma and COVID-19.Cancers · 2023Review
- Role of Midkine in Cancer Drug Resistance: Regulators of Its Expression and Its Molecular Targeting.International journal of molecular sciences · 2023Review
- Midkine inhibition enhances anti-PD-1 immunotherapy in sorafenib-treated hepatocellular carcinoma via preventing immunosuppressive MDSCs infiltration.Cell death discovery · 2023Article
- Review
- Midkine noncanonically suppresses AMPK activation through disrupting the LKB1-STRAD-Mo25 complex.Cell death & disease · 2022Article
- Into the Tissues: Extracellular Matrix and Its Artificial Substitutes: Cell Signalling Mechanisms.Cells · 2022Review
- Circulating Tumour Cells (CTCs) in NSCLC: From Prognosis to Therapy Design.Pharmaceutics · 2021Review
- Slow Off-Rate Modified Aptamer (SOMAmer) Proteomic Analysis of Patient-Derived Malignant Glioma Identifies Distinct Cellular Proteomes.International journal of molecular sciences · 2021Article
- EGFL7 as a novel therapeutic candidate regulates cell invasion and anoikis in colorectal cancer through PI3K/AKT signaling pathway.International journal of clinical oncology · 2021Article
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Midkine is overexpressed in hepatocellular carcinoma (HCC) and plays a role in tumor progression, but less is known about its role in resistance of circulating tumor cells (CTCs) to anoikis which leading to recurrence and metastasis. The aim of the present study was to analyze whether midkine was associated with HCC progression with anoikis resistance. We found that cultured HCC cells were more resistant to anoikis, which paralleled midkine expression, and midkine treatment significantly inhibited anoikis in a dose-dependent manner. Furthermore, in in vitro and in vivo assays, knockdown of midkine resulted in significant sensitivity to anoikis, decreased cell survival and significantly decreased tumor occurrence rate. Patients with midkine-elevated HCC had higher CTC counts and less apoptotic CTCs, as well as significantly higher recurrence rate and shorter recurrence-free interval. To understand the molecular mechanism underlying the midkine with HCC progression, we performed in vitro and in vivo studies. We found that midkine plays an important role in enhancement of HCC cell resistance to anoikis, thereby promoting subsequent metastasis. Activation of PI3K/Akt/NF-κB/TrkB signaling by midkine-activated anaplastic lymphomakinase (ALK) is responsible for anoikis 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.