ArticleCell death and differentiation2021
KPNB1-mediated nuclear translocation of PD-L1 promotes non-small cell lung cancer cell proliferation via the Gas6/MerTK signaling pathway.
Article in Cell death and differentiation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers.
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Who cites it
91 citing papers in PubMed, 205 citations in OpenAlex.
- PD-L1 in Ovarian Cancer: Immune Evasion, Tumor-Intrinsic Signaling, and Chemoresistance.Cancer medicine · 2026Review
- T Cell-Independent Role of PD-L1 in Kidney Repair: Mitigation of Tubular DNA Damage via PD-L1/BRCA1 Interaction Following AKI.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Nuclear PD-L1: an emerging oncogenic driver and promising therapeutic target in cancer.Journal of biomedical science · 2026Review
- Review
- SERBP1 is required for efficient HR repair and cisplatin chemoresistance in lung adenocarcinoma.Cell death discovery · 2026Article
- Tumor-Intrinsic PD-L1 Promotes Breast Cancer Proliferation Through Livin and Galectin-1-Mediated Regulation of SKP2 Expression.International journal of molecular sciences · 2026Article
- Kukoamine B Inhibits EMT in Lung Adenocarcinoma Cells by Regulating Intracellular PD-L1-Mediated p65 Nuclear Translocation.Biology · 2026Article
- Intracellular PD-L1: Functions, Regulation, and Therapeutic Implications.International journal of biological sciences · 2026Review
- Analysis of PD-L1 Transcriptional Activity by Chromatin Immunoprecipitation.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Evaluating Nuclear Levels of PD-L1 in Ovarian Cancer Cells by Western Blotting.Methods in molecular biology (Clifton, N.J.) · 2026Article
- In Situ Assembly of Transformable Monopeptide on Activated Neutrophils Attenuates NETs-Induced Hepatocellular Carcinoma Metastasis by Disrupting NE Nuclear Translocation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Lack of cytoplasmic expression of a new marker programmed cell death ligand-1 in tumor cells is significant.World journal of experimental medicine · 2025Article
- Nuclear PD-L1 drives IFN-γ-promoted lung metastasis of triple-negative breast cancer via POLR2A-mediated transcriptional activation of LY6E.Breast cancer research : BCR · 2025Article
- Integrated analysis of the oncogenic value of CPNE3 in non-small cell lung cancer.Discover oncology · 2025Article
- Article
- Gpr109A in TAMs promoted hepatocellular carcinoma via increasing PKA/PPARγ/MerTK/IL-10/TGFβ induced M2c polarization.Scientific reports · 2025Article
- Review
- Programmed Death-1 Ligand 1 Domain Organization, Signaling Motifs, and Interactors in Cancer Immunotherapy.Cancers · 2025Review
- NADAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Cell-intrinsic PD-L1 signaling drives immunosuppression by myeloid-derived suppressor cells through IL-6/Jak/Stat3 in PD-L1-high lung cancer.Journal for immunotherapy of cancer · 2025Article
31 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In addition to the role of programmed cell death ligand 1 (PD-L1) in facilitating tumour cells escape from immune surveillance, it is considered as a crucial effector in transducing intrinsic signals to promote tumour development. Our previous study has pointed out that PD-L1 promotes non-small cell lung cancer (NSCLC) cell proliferation, but the mechanism remains elusive. Here we first demonstrated that PD-L1 expression levels were positively correlated with p-MerTK levels in patient samples and NSCLC cell lines. In addition, PD-L1 knockdown led to the reduced phosphorylation level of MerTK in vitro. We next showed that PD-L1 regulated NSCLC cell proliferation via Gas6/MerTK signaling pathway in vitro and in vivo. To investigate the underlying mechanism, we unexpectedly found that PD-L1 translocated into the nucleus of cancer cells which was facilitated through the binding of Karyopherin β1 (KPNB1). Nuclear PD-L1 (nPD-L1), coupled with transcription factor Sp1, regulated the synthesis of Gas6 mRNA and promoted Gas6 secretion to activate MerTK signaling pathway. Taken together, our results shed light on the novel role of nPD-L1 in NSCLC cell proliferation and reveal a new molecular mechanism underlying nPD-L1-mediated Gas6/MerTK signaling activation. All above findings provide the possible combinational implications for PD-L1 targeted immunotherapy in the clinic.
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