ArticleCell death & disease2024
MAL2 reprograms lipid metabolism in intrahepatic cholangiocarcinoma via EGFR/SREBP-1 pathway based on single-cell RNA sequencing.
Article in Cell death & disease, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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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.
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Who cites it
19 citing papers in PubMed.
- Review
- Advances in the Molecular Mechanisms of Cholangiocarcinoma: A Comprehensive Review of Biomarkers, Regulatory Pathways and Tumor Microenvironment Reprogramming.International journal of molecular sciences · 2026Review
- Patient-Derived 3D-Bioprinted Intrahepatic Cholangiocarcinoma Models Recapitulate Tumor Autologous Traits and Predict Personalized Adjuvant Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Single-cell transcriptomic mapping of patient-derived primary liver cancer organoids reveals molecular subtypes and guides precision drug targeting.Cellular oncology (Dordrecht, Netherlands) · 2026Article
- Targeting cholesterol metabolism: unlocking new strategies to overcome therapeutic challenges in cholangiocarcinoma.Science China. Life sciences · 2026Article
- Integrative metabolomics and proteomics reveal early cardiovascular risk signatures in PCOS female offspring.Journal of ovarian research · 2026Article
- Integrative Sequencing and Proteogenomic Approaches to Intratumoral Heterogeneity in Cholangiocarcinoma: Implications for Precision Diagnosis and Therapy.Medical sciences (Basel, Switzerland) · 2026Review
- Prognostic Value and Related Molecular Mechanisms of miR-5003-3p in Hepatocellular Carcinoma.Canadian journal of gastroenterology & hepatology · 2026Article
- mTOR signaling in cholangiocarcinoma: mechanistic insights and therapeutic opportunities.Frontiers in pharmacology · 2026Review
- Advances in Multi-Omics Research on Biomarkers of Intrahepatic Cholangiocarcinoma.Current issues in molecular biology · 2025Review
- Precision medicine for advanced biliary tract cancer in China: current status and future perspectives.Frontiers of medicine · 2025Review
- Molecular mechanisms and genetic features of cholangiocarcinoma: implications for targeted therapeutic strategies.Precision clinical medicine · 2025Review
- Urinary Extracellular Vesicle Signatures as Biomarkers in Prostate Cancer Patients.International journal of molecular sciences · 2025Article
- Unlocking the lipid code: SREBPs as key drivers in gastrointestinal tumour metabolism.Lipids in health and disease · 2025Review
- Single-cell RNAseq reveals adverse metabolic transcriptional program in intrahepatic cholangiocarcinoma malignant cells.Biochemistry and biophysics reports · 2025Article
- Multimodal omics analysis of the EGFR signaling pathway in non-small cell lung cancer and emerging therapeutic strategies.Oncology research · 2025Review
- Metabolic collusion driving immune evasion in cholangiocarcinoma: unmasking the dual control of the immuno-metabolic microenvironment.Frontiers in immunology · 2025Review
- Applications of 3D models in cholangiocarcinoma.Frontiers in oncology · 2025Review
- Organoids and spheroids: advancedFrontiers in cell and developmental biology · 2024Review
Corrections and comments
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Authors and funding
12 authors.
Funding
Abstract
Intrahepatic cholangiocarcinoma (ICC) is a highly aggressive cancer characterized by a poor prognosis and resistance to chemotherapy. In this study, utilizing scRNA-seq, we discovered that the tetra-transmembrane protein mal, T cell differentiation protein 2 (MAL2), exhibited specific enrichment in ICC cancer cells and was strongly associated with a poor prognosis. The inhibition of MAL2 effectively suppressed cell proliferation, invasion, and migration. Transcriptomics and metabolomics analyses suggested that MAL2 promoted lipid accumulation in ICC by stabilizing EGFR membrane localization and activated the PI3K/AKT/SREBP-1 axis. Molecular docking and Co-IP proved that MAL2 interacted directly with EGFR. Based on constructed ICC organoids, the downregulation of MAL2 enhanced apoptosis and sensitized ICC cells to cisplatin. Lastly, we conducted a virtual screen to identify sarizotan, a small molecule inhibitor of MAL2, and successfully validated its ability to inhibit MAL2 function. Our findings highlight the tumorigenic role of MAL2 and its involvement in cisplatin sensitivity, suggesting the potential for novel combination therapeutic strategies in ICC.
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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 Socratic graph.