Carregant...
Fitxers
Tipus de document
ArticleVersió
Versió acceptadaData de publicació
Tots els drets reservats
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/172428
PDGFR-induced autocrine SDF-1 signaling in cancer cells promotes metastasis in advanced skin carcinoma
Títol de la revista
Director/Tutor
ISSN de la revista
Títol del volum
Recurs relacionat
Resum
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.
Matèries
Matèries (anglès)
Citació
Citació
BERNAT PEGUERA, Adrià, SIMÓN EXTREMERA, Pilar, DA SILVA-DIZ, Victoria, LÓPEZ DE MUNAIN, Mikel, DÍAZ-GIL, Laura, PENÍN, Rosa maria, GONZÁLEZ-SUÁREZ, Eva, PÉREZ SIDELNIKOVA, Diana, BERMEJO, Oriol, VIÑALS, Joan maria, VIÑALS CANALS, Francesc, MUÑOZ MORUNO, Purificación. PDGFR-induced autocrine SDF-1 signaling in cancer cells promotes metastasis in advanced skin carcinoma. _Oncogene_. 2019. Vol. 38, núm. 25, pàgs. 5021-5037. [consulta: 24 de gener de 2026]. ISSN: 0950-9232. [Disponible a: https://hdl.handle.net/2445/172428]