ArticleJournal of experimental & clinical cancer research : CR2022
AADAC protects colorectal cancer liver colonization from ferroptosis through SLC7A11-dependent inhibition of lipid peroxidation.
Article in Journal of experimental & clinical cancer research : CR, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 52 papers, 1 of them a synthesis that pooled it.
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Who cites it
52 citing papers in PubMed, 1 synthesis or guideline pooled it, 67 citations in OpenAlex.
- A Risk Model Based on Ferroptosis-Related Genes OSMR, G0S2, IGFBP6, IGHG2, and FMOD Predicts Prognosis in Glioblastoma Multiforme.CNS neuroscience & therapeutics · 2025Pooled it
- Rewiring redox defense: Nrf2-driven antioxidant signaling as a gateway to programmed cell death activation in colorectal cancer.Genes & diseases · 2027Review
- Review
- Targeting ferroptosis to overcome drug resistance in gastrointestinal cancers.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- ELAVL1-KO Affects Steroid Synthesis in ACC Cell Line NCI-H295R and Reduces Colony-Forming Abilities.International journal of molecular sciences · 2026Article
- ALOX12 suppresses colon cancer progression by promoting p53-mediated ferroptosis through upregulating ROS-induced stress.Translational cancer research · 2026Article
- Proteomic Analysis Reveals That P97 Inhibitors Induce Ferroptosis in Gastric Cancer AGS Cells.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Multi-omics analysis reveals the alterations in the tumor microbiome and metabolome associated with cervical cancer lymph node metastasis.Microbiology spectrum · 2026Article
- Hesperetin-black phosphorus nanosheets targeting TAMs induce ferroptosis and reverse protumoral polarization to remodel the immune microenvironment.Materials today. Bio · 2026Article
- QSOX1 confers ferroptosis resistance via redox modification of SLC7A11 in colorectal cancer.Cellular & molecular biology letters · 2026Article
- ETV4 promotes colorectal cancer progression through SLC7A11-mediated ferroptosis inhibition.Biology direct · 2026Article
- Review
- Circ_0041150 inhibits proliferation of pancreatic adenocarcinoma cells by regulating triglyceride accumulation via the miR-1178-3p/AADAC axis.Discover oncology · 2026Article
- Ferroptosis and metastasis: molecular checkpoints, microenvironmental dynamics, and therapeutic opportunities.Molecular cancer · 2026Review
- Mechanisms and Drug-Augmenting Strategies of Mesenchymal Stem Cells for Preserving β-Cell in Type 2 Diabetes.Drug design, development and therapy · 2026Review
- The Dual Role of SLC7A11 in Colorectal Cancer Ferroptosis: From Molecular Mechanisms to Therapeutic Opportunities.OncoTargets and therapy · 2026Review
- NRF2 as a ferroptosis gatekeeper in colorectal cancer: implications for therapy.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Targeting ferroptosis in cancer stem cells: A novel strategy to improve cancer treatment.Genes & diseases · 2025Review
- Ferroptosis as a key player in the pathogenesis and intervention therapy in liver injury: focusing on drug-induced hepatotoxicity.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Hyaluronic acid-tailored prodrug nanoplatforms for efficiently overcoming colorectal cancer chemoresistance and recurrence by synergistic inhibition of cancer cell stemness.Journal of nanobiotechnology · 2025Article
Corrections and comments
- Erratum issued
Authors and funding
13 authors at 1 institution in 1 country.
Funding
Abstract
backgroundOxidative stress is a highly active metabolic process in the liver, that poses great threats to disseminated tumor cells during their colonization. Here, we aimed to investigate how colorectal cancer (CRC) cells overcome lipid peroxidation to sustain their metastatic colonization in the liver.
methodsOrthotopic colorectal liver metastasis (CRLM) and CRC liver colonization mouse models were constructed to determine the roles of lipid peroxidation and AADAC in CRC liver colonization. The levels of lipid peroxidation were detected in cells or tissues. AADAC overexpression in LMs and its clinical relevance were analyzed. The oncogenic role of AADAC in CRC liver colonization was evaluated in cell experiments.
resultsCompared with primary tumors (PTs), liver metastases (LMs) showed significantly lower glutathione to oxidized glutathione (GSH/GSSG) ratio and higher malondialdehyde (MDA) levels in CRLM patients and orthotopic mouse models. Inhibition of lipid peroxidation by liproxstatin-1 promoted CRC liver colonization in mouse models. RNA-seq results revealed AADAC as the most significantly upregulated lipid metabolism related gene in LMs compared with PTs. Analyses of datasets and patient and mouse model samples confirmed that AADAC was upregulated in LMs compared with PTs, and was correlated with poor prognosis. AADAC promoted cell proliferation, and facilitated liver colonization in a mouse model by reducing ROS accumulation, which led to lipid peroxidation and ferroptosis. Mechanistically, AADAC upregulated SLC7A11 by activating NRF2 to inhibit lipid peroxidation, thereby protecting metastatic cells from ferroptosis.
conclusionsAADAC protects metastatic CRC cells from ferroptosis by inhibiting lipid peroxidation in an SLC7A11-dependent manner, thus effectively promoting their metastatic colonization and growth in the liver. Together, our findings suggest that AADAC can act as a prognostic indicator and potential therapeutic target for CRLM.
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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.