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Title

Snail1-dependent activation of cancer-associated fibroblast controls epithelial tumor cell invasion and metastasis.

Other TitlesSnail1 controls cancer-associated fibroblast action on tumor cell invasion and metastasis
EMT-independent Snail1 modulation of tumor invasion
AuthorsAlba-Castellón, L.; Olivera, Rubén; Mestre, Aida; Peña, Raúl; Herrera, Mercedes; Bonilla, Félix; Baulida, Josep; Casal, J. Ignacio ; Peña, Cristina; García de Herreros, Antonio
KeywordsSnail1
PGE2
Fibroblast activation
TGF-B
Tumor invasion
Issue Date1-Nov-2016
PublisherAmerican Association for Cancer Research
CitationCancer Res. 76(21):6205-6217 (2016)
AbstractSnail1 transcriptional factor is essential for triggering epithelial-to-mesenchymal transition (EMT) and inducing tumor cell invasion. We report here an additional, EMTindependent action of Snail1 on tumor invasion: its expression in cancer-associated fibroblasts is necessary for enhancement by these cells on epithelial cells tumor invasion. Snail1 expression in fibroblast requires signals derived from tumor cells such as TGF-; reciprocally, in fibroblasts Snail1 organizes a complex program that favors collective invasion of epithelial cells at least in part by the secretion of diffusible signaling molecules, such as prostaglandin E2. The capability of human or murine tumor-derived cancer associated fibroblasts to promote tumor invasion is associated to Snail1 expression and obliterated by Snail1 depletion. In vivo experiments show that Snail1 depletion in mice prevents the invasion of breast tumors and epithelial tumor cells co-xenografted with Snail1-depleted fibroblasts originate tumors with lower invasion than those transplanted with control fibroblasts. Therefore, these results demonstrate that the role of Snail1 in tumor invasion is not limited to EMT but dependent on its expression in stromal fibroblasts where it orchestrates its activation and the crosstalk with epithelial tumor cells. Moreover, they point to the interference of Snail expression as a promising target for preventing the action of stromal fibroblasts on tumor progression.
Description40 p.-6 fig.
Publisher version (URL)http://dx.doi.org/10.1158/0008-5472.CAN-16-0176
URIhttp://hdl.handle.net/10261/158776
DOI10.1158/0008-5472.CAN-16-0176
ISSN0008-5472
E-ISSN1538-7445
Appears in Collections:(CIB) Artículos
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