ArticleMolecular cancer2024
Tumor cell-intrinsic MELK enhanced CCL2-dependent immunosuppression to exacerbate hepatocarcinogenesis and confer resistance of HCC to radiotherapy.
Article in Molecular cancer, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
35 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Limitations of nomogram models in predicting survival outcomes for glioma patients.Frontiers in immunology · 2025Pooled it
- Targeted co-delivery of docetaxel and plumbagin via oxidative priming enhances chemoradiotherapy in non-small cell lung cancer.Materials today. Bio · 2026Article
- Remodelling the tumour microenvironment and beyond: ERO1A as a multifaceted regulator and emerging therapeutic target in cancer.Clinical and translational medicine · 2026Review
- Phosphosite-specific co-regulation networks of MELK kinase: insights from integrative global phosphoproteomes.Journal, genetic engineering & biotechnology · 2026Article
- Article
- ZG16 represses tumor progression and M2 polarization of tumor-associated macrophages in hepatocellular carcinoma by promoting ubiquitination and degradation of SNX9 via binding to ITCH.Hepatology international · 2026Article
- Liver Kinase B1 in CD11cAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Identification of Bruceine A as a novel HSP90AB1 inhibitor for suppressing hepatocellular carcinoma growth.Journal of advanced research · 2026Article
- Spatiotemporal dynamics of radioresistance: decoding macrophage-driven radioprotective niches through temporal-spatial reprogramming.Molecular cancer · 2026Review
- Deciphering the intratumor microbiota in malignant gastrointestinal tumors: multifaceted interplay and clinical implications.Cell communication and signaling : CCS · 2026Review
- Maternal Embryonic Leucine Zipper Kinase (Biology · 2026Review
- Current Perspectives on Radiosensitizers in Cancer Radiotherapy.International journal of nanomedicine · 2026Review
- Comprehensive characterization of SLC41A3 identifies it as an immune-related prognostic biomarker and therapeutic target in hepatocellular carcinoma.Frontiers in immunology · 2026Article
- The link between macrophage polarization and response to radiotherapy in cancers: mechanisms and therapeutic opportunities.Frontiers in immunology · 2026Review
- Transarterial Chemoembolization Modulates the Exosomal miR-32-5p/cGAS-STING Axis Mediated Macrophage Ferroptosis, Triggers Immune Remodeling, and Enhances Anti-PD-1/L1 Efficacy in HCC.Research (Washington, D.C.) · 2026Article
- The role of MELK in cancer: mechanisms and therapeutic options.Frontiers in oncology · 2026Review
- New understanding of the molecular pathogenesis and therapeutic progress of hepatocellular carcinoma.Oncology reviews · 2026Review
- MicroRNA-targeted reprogramming of CD8+ T cells against cancer.Frontiers in immunology · 2026Review
- Tumor-associated endothelial cells in tumor immune escape and immunotherapy: multifaceted roles and treatment approaches.Biomarker research · 2025Review
- Distinct functional heterogeneity of TP53 R175 mutations in platinum-resistant ovarian cancer: unveiling molecular mechanisms and therapeutic targets.Cell death & disease · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors.
Funding
Abstract
backgroundThe outcome of hepatocellular carcinoma (HCC) is limited by its complex molecular characteristics and changeable tumor microenvironment (TME). Here we focused on elucidating the functional consequences of Maternal embryonic leucine zipper kinase (MELK) in the tumorigenesis, progression and metastasis of HCC, and exploring the effect of MELK on immune cell regulation in the TME, meanwhile clarifying the corresponding signaling networks.
methodsBioinformatic analysis was used to validate the prognostic value of MELK for HCC. Murine xenograft assays and HCC lung metastasis mouse model confirmed the role of MELK in tumorigenesis and metastasis in HCC. Luciferase assays, RNA sequencing, immunopurification-mass spectrometry (IP-MS) and coimmunoprecipitation (CoIP) were applied to explore the upstream regulators, downstream essential molecules and corresponding mechanisms of MELK in HCC.
resultsWe confirmed MELK to be a reliable prognostic factor of HCC and identified MELK as an effective candidate in facilitating the tumorigenesis, progression, and metastasis of HCC; the effects of MELK depended on the targeted regulation of the upstream factor miR-505-3p and interaction with STAT3, which induced STAT3 phosphorylation and increased the expression of its target gene CCL2 in HCC. In addition, we confirmed that tumor cell-intrinsic MELK inhibition is beneficial in stimulating M1 macrophage polarization, hindering M2 macrophage polarization and inducing CD8 + T-cell recruitment, which are dependent on the alteration of CCL2 expression. Importantly, MELK inhibition amplified RT-related immune effects, thereby synergizing with RT to exert substantial antitumor effects. OTS167, an inhibitor of MELK, was also proven to effectively impair the growth and progression of HCC and exert a superior antitumor effect in combination with radiotherapy (RT).
conclusionsAltogether, our findings highlight the functional role of MELK as a promising target in molecular therapy and in the combination of RT therapy to improve antitumor effect for HCC.
Indexed as
Identifiers
What OpenQuestion holds
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.