ArticleJournal of cellular physiology2012
Inhibition of lung cancer growth: ATP citrate lyase knockdown and statin treatment leads to dual blockade of mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3-kinase (PI3K)/AKT pathways.
Article in Journal of cellular physiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers, 2 of them syntheses that pooled it.
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
82 citing papers in PubMed, 2 syntheses or guidelines pooled it, 163 citations in OpenAlex.
- Statin use and prognosis of lung cancer: a systematic review and meta-analysis of observational studies and randomized controlled trials.Drug design, development and therapy · 2019Pooled it
- Statin use and risk of lung cancer: a meta-analysis of observational studies and randomized controlled trials.PloS one · 2013Pooled it
- Metabolic reprogramming in colorectal cancer: Mechanisms and therapeutic insights.Genes & diseases · 2027Review
- Lipid Metabolic Reprogramming in Lung Cancer: Mechanisms and Therapeutic Targets in the Tumor Microenvironment.International journal of cancer · 2026Review
- Hallmarks of epithelial-mesenchymal plasticity in cancer.Molecular cancer · 2026Review
- Review
- Metals in the human liver: An underappreciated risk factor of hepatic insulin resistance and associated pathophysiology.Environmental pollution (Barking, Essex : 1987) · 2025Review
- Article
- Statins as potential adjuvant therapy in lung cancer: a narrative review.Journal of thoracic disease · 2025Review
- Increasing cisplatin exposure promotes small-cell lung cancer transformation after a shift from glucose metabolism to fatty acid metabolism.Journal of cancer research and clinical oncology · 2025Article
- Metabolic reprogramming and immunological changes in the microenvironment of esophageal cancer: future directions and prospects.Frontiers in immunology · 2025Review
- Crosstalk between lipid metabolism and EMT: emerging mechanisms and cancer therapy.Molecular and cellular biochemistry · 2025Article
- Role of ATP citrate lyase and its complementary partner on fatty acid synthesis in gastric cancer.Scientific reports · 2024Article
- The impact of epithelial-mesenchymal transition (EMT) induced by metabolic processes and intracellular signaling pathways on chemo-resistance, metastasis, and recurrence in solid tumors.Cell communication and signaling : CCS · 2024Review
- The prognostic value and its relationship with immune infiltration of ACLY in clear cell renal cell carcinoma.Translational oncology · 2024Article
- ATP Citrate Lyase is a General Tumour Biomarker and Contributes to the Development of Cutaneous Squamous Cell Carcinoma.Acta dermato-venereologica · 2024Article
- SIRT2-mediated deacetylation of ACLY promotes the progression of oesophageal squamous cell carcinoma.Journal of cellular and molecular medicine · 2024Article
- Caffeic acid 3,4-dihydroxyphenethyl ester prevents colorectal cancer through inhibition of multiple cancer-promoting signal pathways in 1,2-Dimethylhydrazine/dextran sodium sulphate mouse model.Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan · 2024Article
- Histone deacetylase inhibitor belinostat regulates metabolic reprogramming in killing KRAS-mutant human lung cancer cells.Molecular carcinogenesis · 2023Article
- Investigating potential anti-proliferative activity of different statins against five cancer cell lines.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2023Article
22 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
ATP citrate lyase (ACL) catalyzes the conversion of cytosolic citrate to acetyl-CoA and oxaloacetate. A definitive role for ACL in tumorigenesis has emerged from ACL RNAi and chemical inhibitor studies, showing that ACL inhibition limits tumor cell proliferation and survival and induces differentiation in vitro. In vivo, it reduces tumor growth leading to a cytostatic effect and induces differentiation. However, the underlying molecular mechanisms are poorly understood and agents that could enhance the efficacy of ACL inhibition have not been identified. Our studies focus on non-small cell lung cancer (NSCLC) lines, which show phosphatidylinositol 3-kinase (PI3K)/AKT activation secondary to a mutation in the K-Ras gene or the EGFR gene. Here we show that ACL knockdown promotes apoptosis and differentiation, leading to the inhibition of tumor growth in vivo. Moreover, in contrast to most studies, which elucidate how activation/suppression of signaling pathways can modify metabolism, we show that inhibition of a metabolic pathway "reverse signals" and attenuates PI3K/AKT signaling. Additionally, we find that statins, inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, which act downstream of ACL in the cholesterol synthesis pathway, dramatically enhance the anti-tumor effects of ACL inhibition, even regressing established tumors. With statin treatment, both PI3K/AKT and the MAPK pathways are affected. Moreover, this combined treatment is able to reduce the growth of EGF receptor resistant tumor cell types. Given the essential role of lipid synthesis in numerous cancers, this work may impact therapy in a broad range of tumors.
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.