ArticleMolecular therapy : the journal of the American Society of Gene Therapy2022
An SCD1-dependent mechanoresponsive pathway promotes HCC invasion and metastasis through lipid metabolic reprogramming.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
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Who cites it
68 citing papers in PubMed, 82 citations in OpenAlex.
- The pivotal role of SCD1 in digestive cancers: Bridging lipid metabolic reprogramming and programmed cell death (Review).International journal of oncology · 2026Review
- FTSJ3-Mediated 2'-O-Methylation of HSPA5 mRNA Stabilizes BOP1 via SUMOylation to Drive DRP1-Dependent Mitochondrial Fission and Fatty Acid Oxidation in Lung Squamous Cell Carcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Matrix stiffness drives HCC invasion and metastasis via interfering with TRIM21-mediated SCD1 ubiquitination.Oncogene · 2026Article
- Advances in Lipid Metabolism Reprogramming in Hepatocellular Carcinoma.Journal of clinical and translational hepatology · 2026Review
- FN1 Knockout Inhibits Tumorigenesis but Promotes Lung Metastasis in Hepatocellular Carcinoma.Journal of clinical and translational hepatology · 2026Article
- The RPS15-DDX21 complex drives prostate malignancy through transcriptional activation of SCD1.Oncogene · 2026Article
- [Mechanism ofNan fang yi ke da xue xue bao = Journal of Southern Medical University · 2026Article
- Glucose restriction reprograms lipid metabolism and enhances immunotherapy through ZNRF3-Wnt-SCD signaling axis.Journal for immunotherapy of cancer · 2026Article
- Extracellular Matrix-Related Gene Signature Implied Immunosuppressive Status and Adverse Survival in Diffuse Glioma Patients.Cancers · 2026Article
- The role of e3 ubiquitin ligases and deubiquitinating enzymes in hepatocellular carcinoma.Cell biology and toxicology · 2026Review
- Research progress and therapeutic strategies in hepatocellular carcinoma metabolic reprogramming.Journal of advanced research · 2026Review
- ESM1 drives cancer angiogenesis and bevacizumab resistance via trioleate synthesis.Neoplasia (New York, N.Y.) · 2026Article
- SCD1 licenses STING signaling through fatty acid desaturation-mediated membrane remodeling.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- [Research advances of magnetic resonance elastography for assessing the bioinvasiveness in hepatocellular carcinoma].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2026Review
- Endoplasmic reticulum stress induced autophagy alters cellular processing of cationic lipid delivered siRNAs.Drug delivery and translational research · 2026Article
- Metabolic reprogramming in cancer: dysregulation of glucose, lipid, and amino acid pathways and therapeutic opportunities.Molecular biomedicine · 2026Review
- Review
- Integrin β3 Orchestrates Hepatic Steatosis via a Novel CD36-Dependent Lipid Uptake Complex.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Extracellular matrix stiffness in hepatocellular carcinoma: mechanisms and targeted therapeutic strategies.Frontiers in immunology · 2026Review
- Ultrasound-driven mechanical immunomodulation enhances tumor treatment sensitivity: advances from tumor mechanical immunobiology to immunotherapy applications.Frontiers in immunology · 2026Review
8 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Matrix stiffness promotes hepatocellular carcinoma (HCC) metastasis. This study examined the contribution of lipid metabolic reprogramming to matrix stiffness-induced HCC metastasis. HCC cells were cultured on mechanically tunable polyacrylamide gels and subjected to lipidomic analysis. The key enzyme that responded to matrix stiffness and regulated lipid metabolism was identified. The comparative lipidomic screening revealed that stearoyl-CoA desaturase 1 (SCD1) is a mechanoresponsive enzyme that reprogrammed HCC cell lipid metabolism. The genetic and pharmacological inhibition of SCD1 expression/activity altered the cellular lipid composition, which in turn impaired plasma membrane fluidity and inhibited in vitro invasive motility of HCC cells in response to high matrix stiffness. Knockdown of SCD1 suppressed HCC invasion and metastasis in vivo. Conversely, the overexpression of SCD1 or exogenous administration of its product oleic acid augmented plasma membrane fluidity and rescued in vitro invasive migration in HCC cells cultured on soft substrates, mimicking the effects imposed by high matrix stiffness. In human HCC tissues, collagen content, a marker of increasing matrix stiffness, and increased expression of SCD1 together predicted poor survival of HCC patients. An SCD1-dependent mechanoresponsive pathway that responds to increasing matrix stiffness in the tumor microenvironment promotes HCC invasion and metastasis through lipid metabolic reprogramming.
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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 OpenQuestion graph.