Abstract
Tumors become invasive by penetrating adjacent connective tissue, but the underlying biological mechanisms remain obscure. We recently identified a precise gene expression signature of fibroblastic origin associated with cancer invasion, the first step of the metastatic cascade. The signature contains many coordinately overexpressed genes, prominent among which are COL11A1, THBS2 and INHBA. Here we show that there is a striking similarity between the set of expressed genes in this metastasis-associated fibroblastic (MAF) signature and the set of genes that are downregulated when fibroblasts are reprogrammed to induced pluripotent stem cells (iPSCs). Because it is known that fibroblast reprogramming involves a mesenchymal epithelial transition (MET), the above facts suggest that, conversely, the metastasis-associated fibroblasts responsible for the signature may result from stem-like cells undergoing some type of epithelial-mesenchymal transition (EMT). Therefore, we speculate that cancer stem cells (CSCs) undergoing some type of EMT become fibroblastic to obtain motility and invasiveness, reactivating early embryonic developmental pathways, and that these fibroblast-like cells are the main source of the MAF signature that we previously identified.
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Cheng, Wy., Kim, H., Kandel, J. et al. Cancer invasion associated gene expression signature is present in differentially expressed genes in the reprogramming of fibroblasts into stem cells. Nat Prec (2011). https://doi.org/10.1038/npre.2011.5924.1
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DOI: https://doi.org/10.1038/npre.2011.5924.1