ArticleNature communications2021
Naturally-occurring spinosyn A and its derivatives function as argininosuccinate synthase activator and tumor inhibitor.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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
38 citing papers in PubMed, 73 citations in OpenAlex.
- Metabolism and Immunity-Adapted Radiotherapy (M.I.A.R): A Conceptual Framework for Overcoming the Therapeutic Plateau in Clinical Radiotherapy.Current oncology (Toronto, Ont.) · 2026Review
- The role of the SLC25A15 transporter in the formation of liver metastasis in ESR1-mutated breast cancer.Oncogene · 2026Article
- Harnessing gut microbiota for brain health: protective role of Hungatella hathewayi for post-mTBI cognitive impairment.NPJ biofilms and microbiomes · 2026Article
- L-arginine metabolism in breast cancer: mechanisms and therapeutic targets.Frontiers in oncology · 2026Review
- Model-Guided Systematic Metabolic Engineering for Enhanced Spinosad Biosynthesis in Saccharopolyspora spinosa NHF132.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Evodiamine Inhibits Colorectal Cancer by Downregulating ASS1 via Wnt/β-Catenin/c-MYC Pathway to Block Arginine Synthesis.Pharmaceuticals (Basel, Switzerland) · 2025Article
- BRCAGenie: A machine learning-driven 43-gene polygenic risk score model for precision prediction of breast cancer survival.Journal of translational medicine · 2025Article
- Suyin Detoxification Prescription Regulates the Klotho and ERK/NF-κB Signaling Pathways to Alleviate Renal Injury.Cell biochemistry and biophysics · 2025Article
- ASS1 inhibits liver cancer by promoting CAD ubiquitination and reversing the urea cycle and pyrimidine synthesis imbalance.Hepatology communications · 2025Article
- Invasive lobular carcinoma: integrated multi-omics analysis reveals silencing of Argininosuccinate synthase and upregulation of nucleotide biosynthesis in tamoxifen resistance.Cell death & disease · 2025Article
- Unraveling the therapeutic landscape of approved non-peptide macrocycles.Acta pharmaceutica Sinica. B · 2025Review
- LM2I leads to CAD ubiquitination and liver cancer suppression through activation of ASS1.Acta biochimica et biophysica Sinica · 2025Article
- Intraductal chemotherapy for triple-negative breast cancer: a pathway to minimally invasive clinical treatment.BMC cancer · 2025Article
- Rbfox3 Promotes Transformation of MDSC-Like Tumor Cells to Shape Immunosuppressive Microenvironment.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Integrated multi-omics analysis and machine learning identify G protein-coupled receptor-related signatures for diagnosis and clinical benefits in soft tissue sarcoma.Frontiers in immunology · 2025Article
- Roles of E3 ubiquitin ligases and deubiquitinating enzymes in renal cell carcinoma.Frontiers in oncology · 2025Review
- Enhanced triacylglycerol metabolism contributes to the efficient biosynthesis of spinosad inSynthetic and systems biotechnology · 2024Article
- Temporal Genomic Analysis of Homogeneous Tumor Models Reveals Key Regulators of Immune Evasion in Melanoma.Cancer discovery · 2024Article
- Naphthoquinone-derived ZSW-4B induces apoptosis in triple-negative breast cancer via AMPK signalling activation.Scientific reports · 2024Article
- The therapeutic landscape of citrin deficiency.Journal of inherited metabolic disease · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
24 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Argininosuccinate synthase (ASS1) is a ubiquitous enzyme in mammals that catalyzes the formation of argininosuccinate from citrulline and aspartate. ASS1 genetic deficiency in patients leads to an autosomal recessive urea cycle disorder citrullinemia, while its somatic silence or down-regulation is very common in various human cancers. Here, we show that ASS1 functions as a tumor suppressor in breast cancer, and the pesticide spinosyn A (SPA) and its derivative LM-2I suppress breast tumor cell proliferation and growth by binding to and activating ASS1. The C13-C14 double bond in SPA and LM-2I while the Cys97 (C97) site in ASS1 are critical for the interaction between ASS1 and SPA or LM-2I. SPA and LM-2I treatment results in significant enhancement of ASS1 enzymatic activity in breast cancer cells, particularly in those cancer cells with low ASS1 expression, leading to reduced pyrimidine synthesis and consequently the inhibition of cancer cell proliferation. Thus, our results establish spinosyn A and its derivative LM-2I as potent ASS1 enzymatic activator and tumor inhibitor, which provides a therapeutic avenue for tumors with low ASS1 expression and for those non-tumor diseases caused by down-regulation of ASS1.
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.