ArticleCell communication and signaling : CCS2019
Karyopherin α2-dependent import of E2F1 and TFDP1 maintains protumorigenic stathmin expression in liver cancer.
Article in Cell communication and signaling : CCS, 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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25 citing papers in PubMed, 46 citations in OpenAlex.
- High KPNA2 expression predicts poor prognosis in pathological T4 colorectal cancer by importing c-Myc into the nucleus to suppress p53-dependent p21 expression.British journal of cancer · 2026Article
- A positive feedback loop between KPNA2 and FOXM1 promotes the proliferation of lung adenocarcinoma.European journal of medical research · 2025Article
- [Research progress in the role of STMN1 in tumor].Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2025Review
- Unveiling a novel model of cell senescence-related genes for prognostic assessment and immunotherapeutic insights in gastric cancer.Scientific reports · 2025Article
- Unveiling the link between arsenic toxicity and diabetes: an in silico exploration into the role of transcription factors.Toxicological research · 2024Article
- Identification of two heterogeneous subtypes of hepatocellular carcinoma with distinct pathway activities and clinical outcomes based on gene set variation analysis.Frontiers in genetics · 2024Article
- The role of KPNA2 as a monotonically changing differentially expressed gene in the diagnosis, risk stratification, and chemotherapy sensitivity of chronic hepatitis B-liver cirrhosis-hepatocellular carcinoma.Journal of cancer research and clinical oncology · 2023Article
- Comprehensive Analysis Reveals the Potential Roles of Transcription Factor Dp-1 in Lung Adenocarcinoma.World journal of oncology · 2023Article
- Transcriptome Sequencing Reveals Autophagy Networks in Rat Livers during the Development of NAFLD and Identifies Autophagy Hub Genes.International journal of molecular sciences · 2023Article
- Exploration of the core gene signatures and mechanisms between NAFLD and sarcopenia through transcriptomic level.Frontiers in endocrinology · 2023Article
- STMN1 as a novel prognostic biomarker in HCC correlating with immune infiltrates and methylation.World journal of surgical oncology · 2022Article
- Aberrant Nuclear Translocation of E2F1 and Its Association in Cushing's Disease.Endocrinology · 2022Article
- Article
- Mechanisms of Cell Cycle Arrest and Apoptosis in Glioblastoma.Biomedicines · 2022Review
- HELLS Is Negatively Regulated by Wild-Type P53 in Liver Cancer by a Mechanism Involving P21 and FOXM1.Cancers · 2022Article
- Development of anoikis-related genes signature to predict the prognosis in gastric cancer patients.Frontiers in oncology · 2022Article
- Overexpression of Stathmin 1 Predicts Poor Prognosis and Promotes Cancer Cell Proliferation and Migration in Ovarian Cancer.Disease markers · 2022Article
- HIF-1α-activated long non-coding RNA KDM4A-AS1 promotes hepatocellular carcinoma progression via the miR-411-5p/KPNA2/AKT pathway.Cell death & disease · 2021Article
- PTEN loss promotes oncogenic function of STMN1 via PI3K/AKT pathway in lung cancer.Scientific reports · 2021Article
- A Bioinformatics Analysis Identifies the Telomerase Inhibitor MST-312 for Treating High-STMN1-Expressing Hepatocellular Carcinoma.Journal of personalized medicine · 2021Article
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Authors and funding
13 authors at 6 institutions in 2 countries.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundMembers of the karyopherin superfamily serve as nuclear transport receptors/adaptor proteins and provide exchange of macromolecules between the nucleo- and cytoplasm. Emerging evidence suggests a subset of karyopherins to be dysregulated in hepatocarcinogenesis including karyopherin-α2 (KPNA2). However, the functional and regulatory role of KPNA2 in liver cancer remains incompletely understood.
methodsQuantitative proteomics (LC-MS/MS, ~ 1750 proteins in total) was used to study changes in global protein abundance upon siRNA-mediated KPNA2 knockdown in HCC cells. Functional and mechanistic analyses included colony formation and 2D migration assays, co-immunoprecipitation (CoIP), chromatin immunoprecipitation (ChIP), qRT-PCR, immmunblotting, and subcellular fractionation. In vitro results were correlated with data derived from a murine HCC model and HCC patient samples (3 cohorts, n > 600 in total).
resultsThe proteomic approach revealed the pro-tumorigenic, microtubule (MT) interacting protein stathmin (STMN1) among the most downregulated proteins upon KPNA2 depletion in HCC cells. We further observed that KPNA2 knockdown leads to reduced tumor cell migration and colony formation of HCC cells, which could be phenocopied by direct knockdown of stathmin. As the underlying regulatory mechanism, we uncovered E2F1 and TFDP1 as transport substrates of KPNA2 being retained in the cytoplasm upon KPNA2 ablation, thereby resulting in reduced STMN1 expression. Finally, murine and human HCC data indicate significant correlations of STMN1 expression with E2F1/TFPD1 and with KPNA2 expression and their association with poor prognosis in HCC patients.
conclusionOur data suggest that KPNA2 regulates STMN1 by import of E2F1/TFDP1 and thereby provide a novel link between nuclear transport and MT-interacting proteins in HCC with functional and prognostic significance.
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