Snail1-Dependent Activation of Cancer-Associated Fibroblast Controls Epithelial Tumor Cell Invasion and Metastasis
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- Lorena Alba-Castellón
- 1Programa de Recerca en Càncer, Institut Hospital del Mar d’Investigacions Mèdiques (IMIM), Barcelona, Spain.
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- Rubén Olivera-Salguero
- 1Programa de Recerca en Càncer, Institut Hospital del Mar d’Investigacions Mèdiques (IMIM), Barcelona, Spain.
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- Aida Mestre-Farrera
- 1Programa de Recerca en Càncer, Institut Hospital del Mar d’Investigacions Mèdiques (IMIM), Barcelona, Spain.
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- Raúl Peña
- 1Programa de Recerca en Càncer, Institut Hospital del Mar d’Investigacions Mèdiques (IMIM), Barcelona, Spain.
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- Mercedes Herrera
- 2Servicio de Oncología Médica, Hospital Puerta de Hierro, Majadahonda, Spain.
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- Félix Bonilla
- 3Centro de Estudios Biosanitarios, Madrid, Spain.
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- J. Ignacio Casal
- 4Centro de Investigaciones Biológicas, CSIC, Madrid, Spain.
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- Josep Baulida
- 1Programa de Recerca en Càncer, Institut Hospital del Mar d’Investigacions Mèdiques (IMIM), Barcelona, Spain.
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- Cristina Peña
- 2Servicio de Oncología Médica, Hospital Puerta de Hierro, Majadahonda, Spain.
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- Antonio García de Herreros
- 1Programa de Recerca en Càncer, Institut Hospital del Mar d’Investigacions Mèdiques (IMIM), Barcelona, Spain.
抄録
<jats:title>Abstract</jats:title> <jats:p>Snail1 transcriptional factor is essential for triggering epithelial-to-mesenchymal transition (EMT) and inducing tumor cell invasion. We report here an EMT-independent action of Snail1 on tumor invasion, as it is required for the activation of cancer-associated fibroblasts (CAF). Snail1 expression in fibroblasts requires signals derived from tumor cells, such as TGFβ; reciprocally, in fibroblasts, Snail1 organizes a complex program that stimulates invasion of epithelial cells independent of the expression of Snail1 in these cells. Epithelial cell invasion is stimulated by the secretion by fibroblast of diffusible signaling molecules, such as prostaglandin E2. The capability of human or murine CAFs to promote tumor invasion is dependent on Snail1 expression. Inducible Snail1 depletion in mice decreases the invasion of breast tumors; moreover, epithelial tumor cells coxenografted with Snail1-depleted fibroblasts originated 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 it is also dependent on its activity in stromal fibroblasts, where it orchestrates the cross-talk with epithelial tumor cells. Cancer Res; 76(21); 6205–17. ©2016 AACR.</jats:p>
収録刊行物
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- Cancer Research
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Cancer Research 76 (21), 6205-6217, 2016-10-31
American Association for Cancer Research (AACR)