ArticleCancer research2022
Multiomics Analysis of Spatially Distinct Stromal Cells Reveals Tumor-Induced O-Glycosylation of the CDK4-pRB Axis in Fibroblasts at the Invasive Tumor Edge.
Article in Cancer research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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15 citing papers in PubMed, 42 citations in OpenAlex.
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- Fibroblasts in the tumor microenvironment: heterogeneity and dynamic interactions in tumor progression revealed by spatial transcriptomics.Cellular oncology (Dordrecht, Netherlands) · 2025Review
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- HAS1Journal of experimental & clinical cancer research : CR · 2025Article
- Cancer‑associated fibroblasts: a pivotal regulator of tumor microenvironment in the context of radiotherapy.Cell communication and signaling : CCS · 2025Review
- A quantitative spatial cell-cell colocalizations framework enabling comparisons between in vitro assembloids and pathological specimens.Nature communications · 2025Article
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- Unraveling temporal and spatial biomarkers of epithelial-mesenchymal transition in colorectal cancer: insights into the crucial role of immunosuppressive cells.Journal of translational medicine · 2023Article
- Fibroblast activation protein in the tumor microenvironment predicts outcomes of PD-1 blockade therapy in advanced non-small cell lung cancer.Journal of cancer research and clinical oncology · 2023Article
- QnAs with Carolyn R. Bertozzi.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Artificial intelligence in the analysis of glycosylation data.Biotechnology advances · 2022Review
- The Multiple Roles of CD147 in the Development and Progression of Oral Squamous Cell Carcinoma: An Overview.International journal of molecular sciences · 2022Review
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14 authors at 4 institutions in 2 countries.
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Abstract
The invasive leading edge represents a potential gateway for tumor metastasis. The role of fibroblasts from the tumor edge in promoting cancer invasion and metastasis has not been comprehensively elucidated. We hypothesize that cross-talk between tumor and stromal cells within the tumor microenvironment results in activation of key biological pathways depending on their position in the tumor (edge vs. core). Here we highlight phenotypic differences between tumor-adjacent-fibroblasts (TAF) from the invasive edge and tumor core fibroblasts from the tumor core, established from human lung adenocarcinomas. A multiomics approach that includes genomics, proteomics, and O-glycoproteomics was used to characterize cross-talk between TAFs and cancer cells. These analyses showed that O-glycosylation, an essential posttranslational modification resulting from sugar metabolism, alters key biological pathways including the cyclin-dependent kinase 4 (CDK4) and phosphorylated retinoblastoma protein axis in the stroma and indirectly modulates proinvasive features of cancer cells. In summary, the O-glycoproteome represents a new consideration for important biological processes involved in tumor-stroma cross-talk and a potential avenue to improve the anticancer efficacy of CDK4 inhibitors. SIGNIFICANCE: A multiomics analysis of spatially distinct fibroblasts establishes the importance of the stromal O-glycoproteome in tumor-stroma interactions at the leading edge and provides potential strategies to improve cancer treatment. See related commentary by De Wever, p. 537.
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