ArticleCancer science2022
Nuclear accumulation of KPNA2 impacts radioresistance through positive regulation of the PLSCR1-STAT1 loop in lung adenocarcinoma.
Article in Cancer science, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 21 citations in OpenAlex.
- Customizable host and viral transcript enrichment using CRISPR-Cas9 long-read sequencing for characterization of low-to-moderate abundance isoforms.NAR genomics and bioinformatics · 2026Article
- Integrative multi-omics analysis defines a macrophage-associated phospholipid metabolism signature linked to immune remodeling and prognosis in lung adenocarcinoma.Respiratory research · 2026Article
- PLSCR1 drives chemoresistance in TNBC via METTL3/IGF2BP3-mediated mRNA stabilization and EGFR-MAPK pathway activation.Cell death & disease · 2026Article
- A positive feedback loop between KPNA2 and FOXM1 promotes the proliferation of lung adenocarcinoma.European journal of medical research · 2025Article
- Second allogeneic stem cell transplantation using different donors as the salvage treatment for acute myeloid leukemia relapsed after allogeneic hematopoietic stem cell transplantation.Clinical and experimental medicine · 2025Article
- Targeting the ERK1/2 and p38 MAPK pathways attenuates Golgi tethering factor golgin-97 depletion-induced cancer progression in breast cancer.Cell communication and signaling : CCS · 2025Article
- Machine learning framework develops neutrophil extracellular traps model for clinical outcome and immunotherapy response in lung adenocarcinoma.Apoptosis : an international journal on programmed cell death · 2024Article
- Oxidative stress mediates nucleocytoplasmic shuttling of KPNA2 via AKT1-CDK1 axis-regulated S62 phosphorylation.FASEB bioAdvances · 2024Article
- KPNA2 suppresses porcine epidemic diarrhea virus replication by targeting and degrading virus envelope protein through selective autophagy.Journal of virology · 2023Article
- KPNA2 promotes angiogenesis by regulating STAT3 phosphorylation.Journal of translational medicine · 2022Article
- Phospholipid scramblase 1: a protein with multiple functions via multiple molecular interactors.Cell communication and signaling : CCS · 2022Review
- Nuclear accumulation of KPNA2 impacts radioresistance through positive regulation of the PLSCR1-STAT1 loop in lung adenocarcinoma.Cancer science · 2022Article
- Significance of macrophage infiltration in the prognosis of lung adenocarcinoma patients evaluated by scRNA and bulkRNA analysis.Frontiers in immunology · 2022Article
- Phospholipid Scramblases: Role in Cancer Progression and Anticancer Therapeutics.Frontiers in genetics · 2022Review
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
Abstract
Lung adenocarcinoma (ADC) is the predominant histological type of lung cancer, and radiotherapy is one of the current therapeutic strategies for lung cancer treatment. Unfortunately, biological complexity and cancer heterogeneity contribute to radioresistance development. Karyopherin α2 (KPNA2) is a member of the importin α family that mediates the nucleocytoplasmic transport of cargo proteins. KPNA2 overexpression is observed across cancer tissues of diverse origins. However, the role of KPNA2 in lung cancer radioresistance is unclear. Herein, we demonstrated that high expression of KPNA2 is positively correlated with radioresistance and cancer stem cell (CSC) properties in lung ADC cells. Radioresistant cells exhibited nuclear accumulation of KPNA2 and its cargos (OCT4 and c-MYC). Additionally, KPNA2 knockdown regulated CSC-related gene expression in radioresistant cells. Next-generation sequencing and bioinformatic analysis revealed that STAT1 activation and nuclear phospholipid scramblase 1 (PLSCR1) are involved in KPNA2-mediated radioresistance. Endogenous PLSCR1 interacting with KPNA2 and PLSCR1 knockdown suppressed the radioresistance induced by KPNA2 expression. Both STAT1 and PLSCR1 were found to be positively correlated with dysregulated KPNA2 in radioresistant cells and ADC tissues. We further demonstrated a potential positive feedback loop between PLSCR1 and STAT1 in radioresistant cells, and this PLSCR1-STAT1 loop modulates CSC characteristics. In addition, AKT1 knockdown attenuated the nuclear accumulation of KPNA2 in radioresistant lung cancer cells. Our results collectively support a mechanistic understanding of a novel role for KPNA2 in promoting radioresistance in lung ADC cells.
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