ArticleCell death & disease2019
ASPP2 inhibits tumor growth by repressing the mevalonate pathway in hepatocellular carcinoma.
Article in Cell death & disease, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 31 citations in OpenAlex.
- Mevalonate pathway activation in Ewing sarcoma reveals a 3D-specific synergy between statins and BCL-xL inhibition.Molecular therapy. Oncology · 2026Article
- ASPP2 inhibits hepatocellular carcinoma growth by regulating cuproptosis via mitochondrial protein lipoylation.Cell death & disease · 2026Article
- Simvastatin in liver diseases: therapeutic value and research advances.Clinical and experimental medicine · 2026Review
- SREBP2 regulates CCDC25 expression and promotes tumor metastasis in Triple-Negative Breast Cancer.Oncogenesis · 2026Article
- Unlocking the lipid code: SREBPs as key drivers in gastrointestinal tumour metabolism.Lipids in health and disease · 2025Review
- SREBP2 as a central player in cancer progression: potential for targeted therapeutics.Frontiers in pharmacology · 2025Review
- ASPP2 deficiency promotes the progression of metabolic dysfunction-associated steatohepatitis via ACSL4 upregulation.Scientific reports · 2024Article
- Article
- Lipid Metabolism as a Potential Target of Liver Cancer.Journal of hepatocellular carcinoma · 2024Review
- SREBP Regulation of Lipid Metabolism in Liver Disease, and Therapeutic Strategies.Biomedicines · 2023Review
- Dysregulated cholesterol regulatory genes in hepatocellular carcinoma.European journal of medical research · 2023Review
- TP53BP2: Roles in suppressing tumorigenesis and therapeutic opportunities.Genes & diseases · 2023Review
- mRNA sequencing and CyTOF analysis revealed ASPP2 altered the response patterns of hepatocellular carcinoma HepG2 cells to usnic acid.Naunyn-Schmiedeberg's archives of pharmacology · 2023Article
- ASPP2 suppresses tumour growth and stemness characteristics in HCC by inhibiting Warburg effect via WNT/β-catenin/HK2 axis.Journal of cellular and molecular medicine · 2023Article
- Key events in cancer: Dysregulation of SREBPs.Frontiers in pharmacology · 2023Review
- Gut flora disequilibrium promotes the initiation of liver cancer by modulating tryptophan metabolism and up-regulating SREBP2.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- ASPP2 promotes cell apoptosis in cervical cancer through inhibiting autophagy.Experimental and therapeutic medicine · 2022Article
- Deubiquitinase USP35 stabilizes BRPF1 to activate mevalonate (MVA) metabolism during prostate tumorigenesis.Cell death discovery · 2022Article
- Enhanced CHOLESTEROL biosynthesis promotes breast cancer metastasis via modulating CCDC25 expression and neutrophil extracellular traps formation.Scientific reports · 2022Article
- Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cancer is, fundamentally, a disorder of cell growth and proliferation, which requires adequate supplies of energy and nutrients. In this study, we report that the haplo-insufficient tumor suppressor ASPP2, a p53 activator, negatively regulates the mevalonate pathway to mediate its inhibitory effect on tumor growth in hepatocellular carcinoma (HCC). Gene expression profile analysis revealed that the expression of key enzymes in the mevalonate pathway were increased when ASPP2 was downregulated. HCC cells gained higher cholesterol levels and enhanced tumor-initiating capability in response to the depletion of ASPP2. Simvastatin, a mevalonate pathway inhibitor, efficiently abrogated ASPP2 depletion-induced anchorage-independent cell proliferation, resistance to chemotherapy drugs in vitro, and tumor growth in xenografted nude mice. Mechanistically, ASPP2 interacts with SREBP-2 in the nucleus and restricts the transcriptional activity of SREBP-2 on its target genes, which include key enzymes involved in the mevalonate pathway. Moreover, clinical data revealed better prognosis in patients with high levels of ASPP2 and low levels of the mevalonate pathway enzyme HMGCR. Our findings provide functional and mechanistic insights into the critical role of ASPP2 in the regulation of the mevalonate pathway and the importance of this pathway in tumor initiation and tumor growth, which may provide a new therapeutic opportunity for HCC.
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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.