ArticleScientific reports2024
Single-cell analysis reveals ADGRL4+ renal tubule cells as a highly aggressive cell type in clear cell renal cell carcinoma.
Article in Scientific reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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5 citing papers in PubMed, 3 citations in OpenAlex.
- Review
- aGPCR-HEK: A Stable High-Expression Inducible Mammalian Cell Expression System for Adhesion GPCR Structural Biology Applications.Bio-protocol · 2026Article
- Purification of the Active-State G Protein-Coupled Receptor ADGRL4 for Cryo-Electron Microscopy Using a Modular Tag System and a Tethered mini-GBio-protocol · 2026Article
- Structure of the GNature communications · 2025Article
- BEX4 inhibits the progression of clear cell renal cell carcinoma by stabilizing SH2D4A, which is achieved by blocking SIRT2 activity.Oncogene · 2025Article
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Authors and funding
2 authors at 2 institutions in 1 country.
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Abstract
Clear cell renal cell carcinoma (ccRCC) is a highly heterogeneous cancer that poses great challenge to clinical treatment and prognostic prediction. Characterizing the cellular landscape of ccRCC in a single-cell dimension can help better understand the tumor heterogeneity and molecular mechanisms of ccRCC. This study analyzed single-cell profiles in ccRCC samples and para-tumor samples from Gene Expression Omnibus and identified a highly heterogeneous subcluster of renal tubule cells. Single-cell regulatory network inference and clustering analyses and cell communication analysis were performed to develop transcription factor-target gene regulatory networks and cell-cell interactions. Additionally, the distribution and prognostic risk of renal tubule cells from spatial transcriptome data (GSM6415706) and The Cancer Genome Atlas-Kidney Clear Cell Carcinoma data were analyzed. A total of 10 cell types were identified in ccRCC and para-tumor samples. The ccRCC renal tubule cells showed a high expression of the oncogene nicotinamide N-methyltransferase and a significantly high degree of tumor heterogeneity. We further identified 6 cell subclusters with specific expression of BEX2, PTHLH, SFRP2, KLRB1, ADGRL4, and HGF from the ccRCC renal tubule cells. ADGRL4+ renal tubule cells had highly metastatic and angiogenesis-inducing characteristics, with more ADGRL4+ renal tubule cells indicating a worse survival. ADGRL4+ renal tubule cells regulated the metastasis of other renal tubule cells through metastasis-related receptor-ligand communication. We also found that ADGRL4+ renal tubule cells clustered around the glomeruli but the rest of the renal tubule cell subclusters rarely localized in ccRCC tissues. ETS1 and ELK3 -dominant GRNs were remarkably activated in ADGRL4+ renal tubule cells, functionally, knockdown of ELK3 in A498 significantly disturbedaffected the cell migration and invasion. ADGRL4+ renal tubule cells, which were highly metastatic and invasive, might be an essential cell subcluster for ccRCC, and ADGRL4 could be used a novel therapeutic target.
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