ArticleJournal of experimental & clinical cancer research : CR2019
CDK5-mediated phosphorylation and stabilization of TPX2 promotes hepatocellular tumorigenesis.
Article in Journal of experimental & clinical cancer research : CR, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 39 citations in OpenAlex.
- Cyclins and Cyclin-Dependent Kinases: Structure, Biological Functions, and Innovative Targeting Strategies in Cancer.MedComm · 2026Review
- Leveraging diverse cell-death patterns to predict to predict prognosis and immunotherapy in hepatocellular carcinoma.Discover oncology · 2025Article
- Phosphorylation of USP32 by CDK5 regulates Rap1 stability and therapeutic resistance in pancreatic ductal adenocarcinoma.Oncogene · 2025Article
- Clinical Significance of a Novel Vasculogenic Mimicry-based Prognostic Model in Hepatocellular Carcinoma.Current medicinal chemistry · 2025Article
- Innovative molecular targets for combatting metastasis in adrenocortical carcinoma.Frontiers in endocrinology · 2025Article
- E2F8-TPX2 axis regulates glycolysis and angiogenesis to promote progression and reduce chemosensitivity of liver cancer.Cytotechnology · 2024Article
- Ubiquitin-specific protease 1 facilitates hepatocellular carcinoma progression by modulating mitochondrial fission and metabolic reprogramming via cyclin-dependent kinase 5 stabilization.Cell death and differentiation · 2024Article
- Prognostic value of oxidative phosphorylation-related genes in hepatocellular carcinoma.Discover oncology · 2024Article
- Article
- Exploration of ANKRD27 as an immune-related prognostic factor in pan-cancer and hepatocellular carcinoma.Frontiers in oncology · 2024Article
- Heat shock protein HSPA13 promotes hepatocellular carcinoma progression by stabilizing TANK.Cell death discovery · 2023Article
- CDK5: an oncogene or an anti-oncogene: location location location.Molecular cancer · 2023Review
- Upregulation of helicase-like transcription factor predicts poor prognosis and facilitates hepatocellular carcinoma progression.Human cell · 2023Article
- Transmission of Exosomal TPX2 Promotes Metastasis and Resistance of NSCLC Cells to Docetaxel.OncoTargets and therapy · 2023Article
- Article
- TPX2 regulated by miR-29c-3p induces cell proliferation in osteosarcoma via the AKT signaling pathway.Oncology letters · 2022Article
- Therapeutic Value of Estrogen Receptor α in Hepatocellular Carcinoma Based on Molecular Mechanisms.Journal of clinical and translational hepatology · 2022Review
- Comprehensive Analysis of the Oncogenic Role of Targeting Protein for Xklp2 (TPX2) in Human Malignancies.Disease markers · 2022Article
- The role of hypoxia-related genes in TACE-refractory hepatocellular carcinoma: Exploration of prognosis, immunological characteristics and drug resistance based on onco-multi-OMICS approach.Frontiers in pharmacology · 2022Article
- Identification of a novel histone phosphorylation prognostic signature in hepatocellular carcinoma based on bulk and single-cell RNA sequencing.Frontiers in endocrinology · 2022Article
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundCDK5, an atypical member of the CDK family, play a significant role in the tumorigenesis of multiple organ, but CDK5 and its substrates in genesis and development of HCC is still unclear.
methodsExpression of CDK5 in HCC tumor and paired adjacent noncancerous tissues from 90 patients were measured by Western blotting, immunohistochemistry, and real-time PCR. The role of CDK5 in cell function and tumorigenesis was explored in HCC cell lines, ex vivo xenografts and diethylnitrosamine induced HCC model. Furthermore, comparative phosphoproteomic screening identified the oncoprotein TPX2 as a new substrate of CDK5. We also identified the effect of CDK5/P25 interaction blocker tamoxifen on HCC cell growth and migration.
resultsCDK5 was increased in HCC tisues and the level of CDK5 was correlated with the severity of HCC based on patient recurrence and 5-year fatality rate. Exogenously expressed CDK5 but not kinase-dead CDK5 promoted proliferation, migration, and invasion of HCC cells. Functional ablation of CDK5 significantly inhibited the exacerbation of HCC cells. Xenograft implantation of HCC cells overexpressing CDK5 promoted tumorigenesis, and genetic knockdown of CDK5 reduced HCC growth and metastasis in vivo. More importantly, heterozygous knockout CDK5 (Cdk5+/-) attenuated HCC tumorigenesis induced by diethylnitrosamine. CDK5-mediated phosphorylation of TPX2 at serine 486 promoted its protein stability. TPX2 silence could restore HCC cell migration capability with overexpression CDK5. Treatment with tamoxifen inhibited cell growth and migration of HCC, demonstrating the role of active CDK5 in HCC.
conclusionsOur results suggest activation of CDK5 is associated with HCC tumorigenesis. CDK5-mediated phosphorylation and stabilization of TPX2 promotes hepatocellular proliferation and tumorigenicity.
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