ArticleOncogene2019
Skp2-mediated ubiquitination and mitochondrial localization of Akt drive tumor growth and chemoresistance to cisplatin.
Article in Oncogene, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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The trial behind it
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Who cites it
57 citing papers in PubMed, 99 citations in OpenAlex.
- Exploring the role of protein homeostasis regulation in glycolysis in head and neck tumors.Human cell · 2026Review
- Tumor-associated macrophages suppress estrogen receptor-β expression in triple-negative breast cancer through the PI3K/AKT pathway.Experimental and therapeutic medicine · 2026Article
- SKP2 in Cancer: From Molecular Regulation to Therapeutic Vulnerabilities and Translational Perspectives.Drug design, development and therapy · 2026Review
- Modulation of almonertinib resistance in non-small cell lung cancer by cancer-associated fibroblasts through HK2-mediated glycolysis and SKP2 signaling.Discover oncology · 2025Article
- LKB1 dictates sensitivity to immunotherapy through Skp2-mediated ubiquitination of PD-L1 protein in non-small cell lung cancer.Journal for immunotherapy of cancer · 2024Article
- Endothelial dysfunction: mechanisms and contribution to diseases.Acta pharmacologica Sinica · 2024Review
- Suppression of Skp2 contributes to sepsis-induced acute lung injury by enhancing ferroptosis through the ubiquitination of SLC3A2.Cellular and molecular life sciences : CMLS · 2024Article
- The suppression of HSPA8 attenuates NLRP3 ubiquitination through SKP2 to promote pyroptosis in sepsis-induced lung injury.Cell & bioscience · 2024Article
- Involvement of DJ-1 in the pathogenesis of intervertebral disc degeneration via hexokinase 2-mediated mitophagy.Experimental & molecular medicine · 2024Article
- SP1-activated USP27X-AS1 promotes hepatocellular carcinoma progression via USP7-mediated AKT stabilisation.Clinical and translational medicine · 2024Article
- TRAF4 regulates ubiquitination-modulated survivin turnover and confers radioresistance.International journal of biological sciences · 2024Article
- Survivin degradation by bergenin overcomes pemetrexed resistance.Cellular oncology (Dordrecht, Netherlands) · 2023Article
- E3 ubiquitin ligases in nasopharyngeal carcinoma and implications for therapies.Journal of molecular medicine (Berlin, Germany) · 2023Article
- Function, mechanism and drug discovery of ubiquitin and ubiquitin-like modification with multiomics profiling for cancer therapy.Acta pharmaceutica Sinica. B · 2023Review
- Gastrodin overcomes chemoresistance via inhibiting Skp2-mediated glycolysis.Cell death discovery · 2023Article
- Inhibition of USP14 enhances anti-tumor effect in vemurafenib-resistant melanoma by regulation of Skp2.Cell biology and toxicology · 2023Article
- Targeting survivin with Tanshinone IIA inhibits tumor growth and overcomes chemoresistance in colorectal cancer.Cell death discovery · 2023Article
- Skp2-mediated MLKL degradation confers cisplatin-resistant in non-small cell lung cancer cells.Communications biology · 2023Article
- Roles of protein post-translational modifications in glucose and lipid metabolism: mechanisms and perspectives.Molecular medicine (Cambridge, Mass.) · 2023Review
- SKP2 Contributes to AKT Activation by Ubiquitination Degradation of PHLPP1, Impedes Autophagy, and Facilitates the Survival of Thyroid Carcinoma.Molecules and cells · 2023Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The E3 ligase S-phase kinase-associated protein 2(Skp2) is overexpressed in human cancers and correlated with poor prognosis, but its contributions to tumorigenesis and chemoresistance in nasopharyngeal carcinoma (NPC) are not evident. Herein we show that Skp2 is highly expressed in NPC tumor tissues and cell lines. Knockdown of Skp2 suppresses tumor cell growth, colony formation, glycolysis, and in vivo tumor growth. Skp2 promotes Akt K63-mediated ubiquitination and activation, which is required for EGF-induced Akt mitochondrial localization. Importantly, K63-linked ubiquitination enhances the interaction between Akt and HK2 and eventually increases HK2 phosphorylation on Thr473 and mitochondrial localization. Overexpression of Skp2 impaired the intrinsic apoptotic pathway and confers cisplatin resistance. Moreover, ectopic expression of Myr-Akt1 or phosphomimetic HK2-T473D rescued cisplatin-induced tumor suppression in Skp2 knockdown stable cells. Also, depletion of Akt ubiquitination enhances the antitumor efficacy of cisplatin in vitro and in vivo. Finally, we demonstrated that Skp2 is positively correlated with p-Akt and HK2 in NPC tumor tissues. This study highlights the clinical value of Skp2 targeting in NPC treatment.
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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.