Please use this identifier to cite or link to this item:
Title: PDGFR-induced autocrine SDF-1 signaling in cancer cells promotes metastasis in advanced skin carcinoma
Author: Bernat Peguera, Adrià
Simón Extremera, Pilar
da Silva-Diz, Victoria
López de Munain, Mikel
Díaz-Gil, Laura
Penín, Rosa
González-Suárez, Eva
Pérez Sidelnikova, Diana
Bermejo, Oriol
Viñals, Joan Maria
Viñals Canals, Francesc
Muñoz Moruno, Purificación
Keywords: Càncer de pell
Skin cancer
Issue Date: 15-Mar-2019
Publisher: Macmillan Publishers
Abstract: Advanced and undifferentiated skin squamous cell carcinomas (SCCs) exhibit aggressive growth and enhanced metastasis capability, which is associated in mice with an expansion of the cancer stem-like cell (CSC) population and with changes in the regulatory mechanisms that control the proliferation and invasion of these cells. Indeed, autocrine activation of PDGFRα induces CSC invasion and promotes distant metastasis in advanced SCCs. However, the mechanisms involved in this process were unclear. Here, we show that CSCs of mouse advanced SCCs (L-CSCs) express CXCR4 and CXCR7, both receptors of SDF-1. PDGFRα signaling induces SDF-1 expression and secretion, and the autocrine activation of this pathway in L-CSCs. Autocrine SDF-1/CXCR4 signaling induces L-CSC proliferation and survival, and mediates PDGFRα-induced invasion, promoting in vivo lung metastasis. Validation of these findings in patient samples of skin SCCs shows a strong correlation between the expression of SDF1, PDGFRA, and PDGFRB, which is upregulated, along CXCR4 in tumor cells of advanced SCCs. Furthermore, PDGFR regulates SDF-1 expression and inhibition of SDF-1/CXCR4 and PDGFR pathways blocks distant metastasis of human PD/S-SCCs. Our results indicate that functional crosstalk between PDGFR/SDF-1 signaling regulates tumor cell invasion and metastasis in human and mouse advanced SCCs, and suggest that CXCR4 and/or PDGFR inhibitors could be used to block metastasis of these aggressive tumors.
Note: Versió postprint del document publicat a:
It is part of: Oncogene, 2019, vol. 38, num. 25, p. 5021-5037
Related resource:
ISSN: 0950-9232
Appears in Collections:Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
Articles publicats en revistes (Ciències Fisiològiques)

Files in This Item:
File Description SizeFormat 
692267.pdf7.89 MBAdobe PDFView/Open

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.