We show that glioblastoma multiform (GBM) cells overexpressing the constitutively active form of the epidermal growth factor receptor (EGFRvIII; EGFR+ cells) possess greater invasive properties and have higher levels of extracellular sphingosine-1-phosphate (S1P) and increased sphingosine kinase-1 (SK1) activity than the empty vector-expressing cells. Notably, the inhibition of SK1 or S1P receptors decreases the invasiveness of EGFR+ cells. Moreover, EGFR and MEK1 inhibitors reduce both SK1 activation and cell invasion suggesting that the enhanced invasiveness observed in the EGFR+ cells depends on the increased S1P secretion, downstream of the EGFRvIII-ERK-SK1-S1P pathway. Altogether, our study indicates that in glioblastoma multiform cells, EGFRvIII is connected with the S1P signaling pathway to enhance cell invasiveness and tumor progression.
Crosstalk between sphingosine-1-phosphate and EGFR signalling pathways enhances human glioblastoma cell invasiveness / M.G. Cattaneo, C. Vanetti, M. Samarani, M. Aureli, R. Bassi, S. Sonnino, P. Giussani. - In: FEBS LETTERS. - ISSN 0014-5793. - 592:6(2018 Mar), pp. 949-961. [10.1002/1873-3468.13000]
Crosstalk between sphingosine-1-phosphate and EGFR signalling pathways enhances human glioblastoma cell invasiveness
M.G. Cattaneo;C. Vanetti;M. Samarani;M. Aureli;R. Bassi;S. Sonnino
;P. Giussani
2018
Abstract
We show that glioblastoma multiform (GBM) cells overexpressing the constitutively active form of the epidermal growth factor receptor (EGFRvIII; EGFR+ cells) possess greater invasive properties and have higher levels of extracellular sphingosine-1-phosphate (S1P) and increased sphingosine kinase-1 (SK1) activity than the empty vector-expressing cells. Notably, the inhibition of SK1 or S1P receptors decreases the invasiveness of EGFR+ cells. Moreover, EGFR and MEK1 inhibitors reduce both SK1 activation and cell invasion suggesting that the enhanced invasiveness observed in the EGFR+ cells depends on the increased S1P secretion, downstream of the EGFRvIII-ERK-SK1-S1P pathway. Altogether, our study indicates that in glioblastoma multiform cells, EGFRvIII is connected with the S1P signaling pathway to enhance cell invasiveness and tumor progression.File | Dimensione | Formato | |
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