ArticleProceedings of the National Academy of Sciences of the United States of America2020
A genetically defined disease model reveals that urothelial cells can initiate divergent bladder cancer phenotypes.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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27 citing papers in PubMed, 36 citations in OpenAlex.
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- Modeling glioma intratumoral heterogeneity with primary human neural stem and progenitor cells.Stem cell reports · 2025Article
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- Molecular Characteristics, Heterogeneity, Plasticity, and Cell of Origin of Neuroendocrine Bladder Cancer.Cancer heterogeneity and plasticity · 2025Article
- PGC-1α drives small cell neuroendocrine cancer progression toward an ASCL1-expressing subtype with increased mitochondrial capacity.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- PD-1 blockade plus cisplatin-based chemotherapy in patients with small cell/neuroendocrine bladder and prostate cancers.Cell reports. Medicine · 2024Article
- Role of Forkhead Box P3 in IFNγ-Mediated PD-L1 Expression and Bladder Cancer Epithelial-to-Mesenchymal Transition.Cancer research communications · 2024Article
- Emerging advances in defining the molecular and therapeutic landscape of small-cell lung cancer.Nature reviews. Clinical oncology · 2024Review
- Decoding the basis of histological variation in human cancer.Nature reviews. Cancer · 2024Review
- Temporal evolution reveals bifurcated lineages in aggressive neuroendocrine small cell prostate cancer trans-differentiation.Cancer cell · 2023Article
- Advances in the bladder cancer research using 3D culture models.Bladder (San Francisco, Calif.) · 2023Review
- Replication stress defines distinct molecular subtypes across cancers.Cancer research communications · 2022Article
- Article
- Ex Vivo Organoid Model of Adenovirus-Cre Mediated Gene Deletions in Mouse Urothelial Cells.Journal of visualized experiments : JoVE · 2022Article
- Donor-Derived Urothelial Carcinoma in Renal Transplant Recipients.Case reports in urology · 2022Article
- Construction of heparin-based hydrogel incorporated with Cu5.4O ultrasmall nanozymes for wound healing and inflammation inhibition.Bioactive materials · 2021Article
- A new m6A methylation-related gene signature for prognostic value in patient with urothelial carcinoma of the bladder.Bioscience reports · 2021Article
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18 authors at 2 institutions in 1 country.
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Abstract
Small cell carcinoma of the bladder (SCCB) is a rare and lethal phenotype of bladder cancer. The pathogenesis and molecular features are unknown. Here, we established a genetically engineered SCCB model and a cohort of patient SCCB and urothelial carcinoma samples to characterize molecular similarities and differences between bladder cancer phenotypes. We demonstrate that SCCB shares a urothelial origin with other bladder cancer phenotypes by showing that urothelial cells driven by a set of defined oncogenic factors give rise to a mixture of tumor phenotypes, including small cell carcinoma, urothelial carcinoma, and squamous cell carcinoma. Tumor-derived single-cell clones also give rise to both SCCB and urothelial carcinoma in xenografts. Despite this shared urothelial origin, clinical SCCB samples have a distinct transcriptional profile and a unique transcriptional regulatory network. Using the transcriptional profile from our cohort, we identified cell surface proteins (CSPs) associated with the SCCB phenotype. We found that the majority of SCCB samples have PD-L1 expression in both tumor cells and tumor-infiltrating lymphocytes, suggesting that immune checkpoint inhibitors could be a treatment option for SCCB. We further demonstrate that our genetically engineered tumor model is a representative tool for investigating CSPs in SCCB by showing that it shares a similar a CSP profile with clinical samples and expresses SCCB-up-regulated CSPs at both the mRNA and protein levels. Our findings reveal distinct molecular features of SCCB and provide a transcriptional dataset and a preclinical model for further investigating SCCB biology.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.