Single-cell analysis reveals the pan-cancer invasiveness-associated transition of adiposederived stromal cells into COL11A1- expressing cancer-associated fibroblasts

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Abstract

During the last ten years, many research results have been referring to a particular type of cancer-associated fibroblasts associated with poor prognosis, invasiveness, metastasis and resistance to therapy in multiple cancer types, characterized by a gene expression signature with prominent presence of genes COL11A1, THBS2 and INHBA. Identifying the underlying biological mechanisms responsible for their creation may facilitate the discovery of targets for potential pan-cancer therapeutics. Using a novel computational approach for single-cell gene expression data analysis identifying the dominant cell populations in a sequence of samples from patients at various stages, we conclude that these fibroblasts are produced by a pan-cancer cellular transition originating from a particular type of adiposederived stromal cells naturally present in the stromal vascular fraction of normal adipose tissue, having a characteristic gene expression signature. Focusing on a rich pancreatic cancer dataset, we provide a detailed description of the continuous modification of the gene expression profiles of cells as they transition from APOD-expressing adipose-derived stromal cells to COL11A1-expressing cancer-associated fibroblasts, identifying the key genes that participate in this transition. These results also provide an explanation to the wellknown fact that the adipose microenvironment contributes to cancer progression. Copyright:

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Zhu, K., Cai, L., Cui, C., De Los Toyos, J. R., & Anastassiou, D. (2021). Single-cell analysis reveals the pan-cancer invasiveness-associated transition of adiposederived stromal cells into COL11A1- expressing cancer-associated fibroblasts. PLoS Computational Biology, 17(7). https://doi.org/10.1371/journal.pcbi.1009228

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