ArticleCancer cell2016
Spontaneous Hepatocellular Carcinoma after the Combined Deletion of Akt Isoforms.
Article in Cancer cell, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers, 1 of them a synthesis that pooled it.
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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.
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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.
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Who cites it
76 citing papers in PubMed, 1 synthesis or guideline pooled it, 113 citations in OpenAlex.
- Evaluating the roles of microRNAs associated with nonalcoholic fatty liver disease in hepatocellular carcinoma tumorigenesis: a systematic review and network analysis.Frontiers in medicine · 2024Pooled it
- PTEN-AKT2 regulates mixed lineage liver cancer development and sensitizes cancer cells to TGFβ treatment.Oncogene · 2026Article
- Loss of intestinal Akt elicits rapid mortality via intestinal damage which is rescued by mTORC1 activation.Nature communications · 2026Article
- Loss of hepatocyte PI3Kα reduces hepatocellular carcinoma and hepatocyte proliferation in association with altered lipid metabolism.JHEP reports : innovation in hepatology · 2026Article
- Fluconazole-induced liver injury in patients with pulmonary cryptococcosis: a comprehensive study integrating clinical cohort analysis, network toxicology, molecular docking, and transcriptomics.Antimicrobial agents and chemotherapy · 2026Article
- Ribosome biogenesis is increased in hepatocellular carcinoma and represents a potential therapeutic target.NAR cancer · 2026Article
- PTEN-AKT2 Regulates Mixed Lineage Liver Cancer Development and Sensitizes Cancer Cells to TGFβ Treatment.Research square · 2026Article
- A Comprehensive Review ofDrug design, development and therapy · 2026Review
- TTLL4 mediates the PI3K/AKT/MDM2 pathway to promote hepatocellular carcinoma progression and predict patient prognosis.APL bioengineering · 2025Article
- SR-A3 suppresses AKT activation to protect against MAFLD by inhibiting XIAP-mediated PTEN degradation.Nature communications · 2025Article
- Wogonoside alleviates the proliferation and promotes the apoptosis in liver cancer cells by regulating PI3K/Akt signaling pathway.Discover oncology · 2025Article
- Hepatocellular carcinoma: signaling pathways and therapeutic advances.Signal transduction and targeted therapy · 2025Review
- AKT inhibitors in gynecologic oncology: past, present and future.Frontiers in oncology · 2025Review
- AKT kinases as therapeutic targets.Journal of experimental & clinical cancer research : CR · 2024Review
- TSC/mTORC1 mediates mTORC2/AKT1 signaling in c-MYC-induced murine hepatocarcinogenesis via centromere protein M.The Journal of clinical investigation · 2024Article
- Complex Roles ofAnnual review of cancer biology · 2024Article
- Understanding the Biological Basis of Polygenic Risk Scores and Disparities in Prostate Cancer: A Comprehensive Genomic Analysis.Cancer informatics · 2024Article
- Decrotonylation of AKT1 promotes AKT1 phosphorylation and activation during myogenic differentiation.Journal of advanced research · 2023Article
- Ginsenoside Rg3 inhibits the malignant progression of cervical cancer cell by regulating AKT2 expression.Heliyon · 2023Article
- CircRNA Circ_0000118 Regulates Malignancy of Cervical Cancer Cells by Regulating miR-211-5p/miR-377-3p/AKT2 Axis.Biochemical genetics · 2023Article
16 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Akt is frequently hyperactivated in human cancers and is targeted for cancer therapy. However, the physiological consequences of systemic Akt isoform inhibition were not fully explored. We showed that while combined Akt1 and Akt3 deletion in adult mice is tolerated, combined Akt1 and Akt2 deletion induced rapid mortality. Akt2(-/-) mice survived hepatic Akt1 deletion but all developed spontaneous hepatocellular carcinoma (HCC), which is associated with FoxO-dependent liver injury and inflammation. The gene expression signature of HCC-bearing livers is similar to aggressive human HCC. Consistently, neither Akt1(-/-) nor Akt2(-/-) mice are resistant to diethylnitrosamine-induced hepatocarcinogenesis, and Akt2(-/-) mice display a high incidence of lung metastasis. Thus, in contrast to other cancers, hepatic Akt inhibition induces liver injury that could promote 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.