ArticleHepatology (Baltimore, Md.)2021
Targeting the De Novo Purine Synthesis Pathway Through Adenylosuccinate Lyase Depletion Impairs Liver Cancer Growth by Perturbing Mitochondrial Function.
Article in Hepatology (Baltimore, Md.), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 34 citations in OpenAlex.
- KRAS Withdrawal in Cholangiocarcinoma Leads to Immune Infiltration and Tumor Regression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Adenylosuccinate lyase in pancreatic ductal adenocarcinoma chemoresistance: from purine metabolism to metabolic vulnerability.Cancer drug resistance (Alhambra, Calif.) · 2026Review
- The inhibition of de novo purine synthesis increases LAMP2 expression to preserve cell viability.Cell death discovery · 2025Article
- The impact of asparaginase phenotype-related single nucleotide polymorphisms on prognosis in pediatric B-cell precursor acute lymphoblastic leukemia.European journal of medical research · 2025Article
- ADSL deficiency is a secondary mitochondrial disease affecting organelle homeostasis and ERK2/AKT signaling in a linear genotype-phenotype relation.Cell reports · 2025Article
- ADSL promotes autophagy and tumor growth through fumarate-mediated Beclin1 dimethylation.Nature chemical biology · 2025Article
- Purinosomes as a therapeutic target in hepatocellular carcinoma: insights and opportunities.Discover oncology · 2025Article
- Alanine supplementation enhancing cordycepin production in Cordyceps militaris via upregulation of Cns2 and Cns3 genes expression levels.Journal of food and drug analysis · 2024Article
- The prevalence of ADSL (rs3788579) and CYP1A2 (rs17861162) polymorphisms in female breast cancer patients in North-West Iran.Discover oncology · 2024Article
- CRISPR in Targeted Therapy and Adoptive T Cell Immunotherapy for Hepatocellular Carcinoma.Journal of hepatocellular carcinoma · 2024Review
- Construction of a ceRNA regulatory network to explore potential pathogenesis mechanisms involved in human hepatocellular carcinoma.Scientific reports · 2023Article
- Donafenib and GSK-J4 Synergistically Induce Ferroptosis in Liver Cancer by Upregulating HMOX1 Expression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Nanoplastics Toxicity Specific to Liver in Inducing Metabolic Dysfunction-A Comprehensive Review.Genes · 2023Review
- Article
- Metabolites of De Novo Purine Synthesis: Metabolic Regulators and Cytotoxic Compounds.Metabolites · 2022Article
- Genome-Wide CRISPR/Cas9 Library Screening Revealed Dietary Restriction of Glutamine in Combination with Inhibition of Pyruvate Metabolism as Effective Liver Cancer Treatment.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- MicroRNA-21 guide and passenger strand regulation of adenylosuccinate lyase-mediated purine metabolism promotes transition to an EGFR-TKI-tolerant persister state.Cancer gene therapy · 2022Article
- Purine Synthesis Inhibitor L-Alanosine Impairs Mitochondrial Function and Stemness of Brain Tumor Initiating Cells.Biomedicines · 2022Article
- LZTR1: A promising adaptor of the CUL3 family.Oncology letters · 2021Review
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
BACKGROUND AND
aimsHepatocellular carcinoma (HCC) is among the most common cancer types worldwide, yet patients with HCC have limited treatment options. There is an urgent need to identify drug targets that specifically inhibit the growth of HCC cells. APPROACH AND
resultsWe used a CRISPR library targeting ~2,000 druggable genes to perform a high-throughput screen and identified adenylosuccinate lyase (ADSL), a key enzyme involved in the de novo purine synthesis pathway, as a potential drug target for HCC. ADSL has been implicated as a potential oncogenic driver in some cancers, but its role in liver cancer progression remains unknown. CRISPR-mediated knockout of ADSL impaired colony formation of liver cancer cells by affecting AMP production. In the absence of ADSL, the growth of liver tumors is retarded in vivo. Mechanistically, we found that ADSL knockout caused S-phase cell cycle arrest not by inducing DNA damage but by impairing mitochondrial function. Using data from patients with HCC, we also revealed that high ADSL expression occurs during tumorigenesis and is linked to poor survival rate.
conclusionsOur findings uncover the role of ADSL-mediated de novo purine synthesis in fueling mitochondrial ATP production to promote liver cancer cell growth. Targeting ADSL may be a therapeutic approach for patients with HCC.
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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.