ArticleTranslational oncology2023
Multiregion single cell analysis reveals a novel subtype of cancer-associated fibroblasts located in the hypoxic tumor microenvironment in colorectal cancer.
Article in Translational oncology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 15 citations in OpenAlex.
- Activin A-Targeted Therapy in Cancer: An Updated Review on Challenges and Opportunities in Clinical Translation.Current pharmaceutical design · 2026Review
- Fibroblasts in the tumor microenvironment: heterogeneity and dynamic interactions in tumor progression revealed by spatial transcriptomics.Cellular oncology (Dordrecht, Netherlands) · 2025Review
- Cancer-associated fibroblasts enhance colorectal cancer lymphatic metastasis via CLEC11A/LGR5-mediated WNT pathway activation.The Journal of clinical investigation · 2025Article
- INHBABMC cancer · 2025Article
- Long non-coding RNA NEAT1 promotes colorectal cancer progression via interacting with SIRT1.Scientific reports · 2025Article
- Consensus clustering and development of a risk signature based on trajectory differential genes of cancer-associated fibroblast subpopulations in colorectal cancer.Journal of cancer research and clinical oncology · 2024Article
- Subpopulations of fibroblasts derived from human iPS cells.Communications biology · 2024Article
- Article
- Intratumoral CXCR4Frontiers in immunology · 2024Article
- Architectural organization and molecular profiling of 3D cancer heterospheroids and their application in drug testing.Frontiers in oncology · 2024Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe tumor microenvironment (TME) plays a critical role in shaping tumor progression and determining the outcome of the therapeutic response. In this study, we aimed to generate a comprehensive cellular landscape of the colorectal cancer (CRC) TME.
methodsWe generated a comprehensive single-cell atlas by collecting CRC cases that have been uploaded to the online database and conducting an in-depth secondary analysis. We then carried out spatial transcriptomic sequencing and multiple immunohistochemical analyses to verify the results of the single-cell analysis. Moreover, we applied our findings to the TCGA database and used tissue microarray (TMA) on CRC tissue specimens to validate clinical prognosis.
findingsWe re-analyzed the transcriptomes of 23785 cells, revealing a pattern of cell heterogeneity in the tumor region, leading-edge region, and non-tumor region. A subtype of COL11A1+INHBA+ tumor-resident cancer-associated fibroblasts (CAFs) was identified, and marker genes, transcription factors, and tissue-specific expression differences were noted and suggested to have potential roles in promoting cancer. We further confirmed that COL11A1+INHBA+ tumor-resident CAFs are mainly located in the hypoxic TME and we propose that they interact with CD44+ CRC cells via INHBA. Elevation of INHBA in CRC is associated with a poor prognosis.
interpretationOur results demonstrated a single cell landscape of CRC in different regions and identified in hypoxic TME a special subtype of CAFs producing INHBA, which promotes CRC development and correlates with poor prognosis. This special subtype of CAFs is a candidate target for translational research.
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