ArticleCell death & disease2019
Osteosarcoma cell intrinsic PD-L2 signals promote invasion and metastasis via the RhoA-ROCK-LIMK2 and autophagy pathways.
Article in Cell death & disease, 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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Who cites it
57 citing papers in PubMed, 83 citations in OpenAlex.
- PD-L1 and PD-L2 regulate in cell-autonomous and N-glycosylation-dependent manners the pro-tumorigenic characteristics and functions of human cancer-associated fibroblasts.Molecular medicine (Cambridge, Mass.) · 2026Article
- PD-L2 Landscape and Correlation with Outcome: An Immunomic Analysis.JCO oncology advances · 2026Article
- Mechanical properties of the tumor microenvironment: drivers of immunotherapy resistance in solid tumors.Frontiers in immunology · 2026Review
- Natural products reshape osteosarcoma cell fate: promoting cell death.Frontiers in pharmacology · 2026Review
- Targeting the osteosarcoma immune microenvironment for improved immunotherapy and translational applications.Discover oncology · 2025Review
- PD-1, PD-L1, and PD-L2 Expression as Predictive Markers in Rare Feline Mammary Tumors.Veterinary sciences · 2025Article
- Radiation suppresses liver metastases via exosome secretion in pancreatic cancer cells.Scientific reports · 2025Article
- Zinc finger DHHC-type palmitoyltransferase 13-mediated S-palmitoylation of GNA13 from Sertoli cell-derived extracellular vesicles inhibits autophagy in spermatogonial stem cells.Cell communication and signaling : CCS · 2025Article
- DCC-2036 inhibits osteosarcoma via targeting HCK and the PI3K/AKT-mTORC1 axis to promote autophagy.World journal of surgical oncology · 2025Article
- High PD-L2 Expression Is Associated with Better Disease-Free Survival in Patients with Intrahepatic Cholangiocarcinoma.Cancer management and research · 2025Article
- High CTLA-4 gene expression is an independent good prognosis factor in breast cancer patients, especially in the HER2-enriched subtype.Cancer cell international · 2024Article
- SPHK1 promotes bladder cancer metastasis via PD-L2/c-Src/FAK signaling cascade.Cell death & disease · 2024Article
- PD-L2 mediates tobacco smoking-induced recruitment of regulatory T cells via the RGMB/NFκB/CCL20 cascade.Cell biology and toxicology · 2024Article
- The role of programmed cell death in osteosarcoma: From pathogenesis to therapy.Cancer medicine · 2024Review
- Article
- The role of stromal cells in epithelial-mesenchymal plasticity and its therapeutic potential.Discover oncology · 2024Review
- VAMP8 suppresses the metastasis via DDX5/β-catenin signal pathway in osteosarcoma.Cancer biology & therapy · 2023Article
- Association of PD-L1 and PD-L2 expression and tumor-infiltrating lymphocytes inESMO gastrointestinal oncology · 2023Article
- WTAP regulates autophagy in colon cancer cells by inhibiting FLNA through N6-methyladenosine.Cell adhesion & migration · 2023Article
- Review
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Known as co-stimulatory molecule, programmed death ligand-2 (PD-L2) contributes to T-cell exhaustion by interaction with programmed death-1 (PD-1) receptor, but its tumor cell-intrinsic signal effects have been little investigated. PD-L2 expression was detected by immunohistochemistry in 18 pairs of primary osteosarcoma tissues and matching lung metastasis tissues. We also investigated the effects of PD-L2 knockdown on osteosarcoma both in vitro and in vivo. In our study, PD-L2 expression was elevated in lung metastases compared with primary osteosarcoma according to an immunohistochemistry assay. Wound-healing and transwell assays revealed that PD-L2 knockdown leaded to inhibition of migration and invasion of human osteosarcoma cells in vitro. Mechanistically, we demonstrated that PD-L2 knockdown attenuated migration and invasion by inactivating RhoA-ROCK-LIMK2 signaling, suppressing epithelial-mesenchymal transition (EMT), and inhibiting autophagy by decreasing beclin-1 expression. In support of these observations, beclin-1 knockdown also inhibited activation of the RhoA-ROCK-LIMK2 pathway, leading to autophagy inhibition-induced blockade of migration and invasion. Depletion of PD-L2 in KHOS cells markedly weakens pulmonary metastatic potential in vivo by orthotopic transplantation of nude mice. Our study reveals a pro-metastatic functional mechanism for PD-L2 in osteosarcoma. Furthermore, we demonstrate a regulatory role for PD-L2 on autophagy, as well as a relationship between autophagy and metastasis in osteosarcoma, which may represent a potential therapeutic target for osteosarcoma.
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