ArticleOncotarget2015
SKP2 cooperates with N-Ras or AKT to induce liver tumor development in mice.
Article in Oncotarget, 2015. 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, 31 citations in OpenAlex.
- Molecular Dynamics Simulation-Assisted siRNA Design for Dual-Ubiquitinated SKP2 Silencing via Ago2 Anchoring in Breast Cancer.ACS omega · 2026Article
- Mechanisms of HRAS regulation of liver hepatocellular carcinoma for prognosis prediction.BMC cancer · 2025Article
- Fatty Acid Synthase Promotes Hepatocellular Carcinoma Growth via S-Phase Kinase-Associated Protein 2/p27Medicina (Kaunas, Lithuania) · 2024Article
- Development of a prognostic model for anoikis and identifies hub genes in hepatocellular carcinoma.Scientific reports · 2023Article
- PIK3R3 is upregulated in liver cancer and activates Akt signaling to control cancer growth by regulation of CDKN1C and SMC1A.Cancer medicine · 2023Article
- Targeting Akt in Hepatocellular Carcinoma and Its Tumor Microenvironment.International journal of molecular sciences · 2021Review
- GINS1 Induced Sorafenib Resistance by Promoting Cancer Stem Properties in Human Hepatocellular Cancer Cells.Frontiers in cell and developmental biology · 2021Article
- Comparative Analysis on Abnormal Methylome of Differentially Expressed Genes and Disease Pathways in the Immune Cells of RA and SLE.Frontiers in immunology · 2021Article
- S-Phase Kinase-associated Protein-2 Rejuvenates Senescent Endothelial Progenitor Cells and Induces Angiogenesis in Vivo.Scientific reports · 2020Article
- Paeoniflorin inhibits cell viability and invasion of liver cancer cells via inhibition of Skp2.Oncology letters · 2020Article
- HBx regulates transcription factor PAX8 stabilization to promote the progression of hepatocellular carcinoma.Oncogene · 2019Article
- Review
- Functional role of SGK3 in PI3K/Pten driven liver tumor development.BMC cancer · 2019Article
- Ubiquitin ligases in oncogenic transformation and cancer therapy.Nature reviews. Cancer · 2018Review
- Loss of Pten synergizes with c-Met to promote hepatocellular carcinoma development via mTORC2 pathway.Experimental & molecular medicine · 2018Article
- Dual inhibition of BRD4 and PI3K-AKT by SF2523 suppresses human renal cell carcinoma cell growth.Oncotarget · 2017Article
- Targeting β-catenin in hepatocellular cancers induced by coexpression of mutant β-catenin and K-Ras in mice.Hepatology (Baltimore, Md.) · 2017Article
- Co-activation of AKT and c-Met triggers rapid hepatocellular carcinoma development via the mTORC1/FASN pathway in mice.Scientific reports · 2016Article
- Co-activation of PIK3CA and Yap promotes development of hepatocellular and cholangiocellular tumors in mouse and human liver.Oncotarget · 2015Article
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
Abstract
Mounting evidence indicates that S-Phase Kinase-Associated Protein 2 (SKP2) is overexpressed in human hepatocellular carcinoma (HCC). However, the role of SKP2 in hepatocarcinogenesis remains poorly delineated. To elucidate the function(s) of SKP2 in HCC, we stably overexpressed the SKP2 gene in the mouse liver, either alone or in combination with activated forms of N-Ras (N-RasV12), AKT1 (myr-AKT1), or β-catenin (ΔN90-β-catenin) protooncogenes, via hydrodynamic gene delivery. We found that forced overexpression of SKP2, N-RasV12 or ΔN90-β-catenin alone as well as co-expression of SKP2 and ΔN90-β-catenin did not induce liver tumor development. Overexpression of myr-AKT1 alone led to liver tumor development after long latency. In contrast, co-expression of SKP2 with N-RasV12 or myr-AKT1 resulted in early development of multiple hepatocellular tumors in all SKP2/N-RasV12 and SKP2/myr-AKT1 mice. At the molecular level, preneoplastic and neoplastic liver lesions from SKP2/N-RasV12 and SKP2/myr-AKT1 mice exhibited a strong induction of AKT/mTOR and Ras/MAPK pathways. Noticeably, the tumor suppressor proteins whose levels have been shown to be downregulated by SKP2-dependent degradation in various tumor types, including p27, p57, Dusp1, and Rassf1A were not decreased in liver lesions from SKP2/N-RasV12 and SKP2/myr-AKT1 mice. In human HCC specimens, nuclear translocation of SKP2 was associated with activation of the AKT/mTOR and Ras/MAPK pathways, but not with β-catenin mutation or activation. Altogether, the present data indicate that SKP2 cooperates with N-Ras and AKT proto-oncogenes to promote hepatocarcinogenesis in vivo.
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