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Cross-talk Between sphingosine-1-phosphate and EGFR Signaling Pathways Enhances Human Glioblastoma Cell Invasiveness

Cross-talk Between sphingosine-1-phosphate and EGFR Signaling Pathways Enhances Human Glioblastoma Cell Invasiveness

Maria Grazia Cattaneo, Claudia Vanetti, Maura Samarani, Massimo Aureli, Rosaria Bassi, Sandro Sonnino, Paola Giussani

FEBS Lett. 2018 Mar;592(6):949-961.

PMID: 29427528

Abstract:

We show that glioblastoma multiform (GBM) cells overexpressing the constitutively active form of the epidermal growth factor receptor [epidermal growth factor receptor variant III (EGFRvIII) and U87MG human GBM cell line overexpressing 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, the results of the present study indicate that, in GBM cells, EGFRvIII is connected with the S1P signaling pathway to enhance cell invasiveness and tumor progression.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR42416148	Sphingosine kinase 1 Active human			Price

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