Radiation Increases Functional KCa3.1 Expression and Invasiveness in Glioblastoma.
Giuseppina D'AlessandroLucia MonacoLuigi CatacuzzenoFabrizio AntonangeliAntonio SantoroVincenzo EspositoFabio FrancioliniHeike WulffCristina LimatolaPublished in: Cancers (2019)
Glioblastoma (GBM) is a deadly brain tumor, with fast recurrence even after surgical intervention, radio- and chemotherapies. One of the reasons for relapse is the early invasion of surrounding brain parenchyma by GBM, rendering tumor eradication difficult. Recent studies demonstrate that, in addition to eliminate possible residual tumoral cells after surgery, radiation stimulates the infiltrative behavior of GBM cells. The intermediate conductance of Ca2+-activated potassium channels (KCa3.1) play an important role in regulating the migration of GBM. Here, we show that high dose radiation of patient-derived GBM cells increases their invasion, and induces the transcription of key genes related to these functions, including the IL-4/IL-4R pair. In addition, we demonstrate that radiation increases the expression of KCa3.1 channels, and that their pharmacological inhibition counteracts the pro-invasive phenotype induced by radiation in tumor cells. Our data describe a possible approach to treat tumor resistance that follows radiation therapy in GBM patients.
Keyphrases
- induced apoptosis
- cell cycle arrest
- radiation therapy
- high dose
- poor prognosis
- radiation induced
- randomized controlled trial
- ejection fraction
- cell death
- end stage renal disease
- squamous cell carcinoma
- low dose
- dna methylation
- signaling pathway
- free survival
- helicobacter pylori infection
- white matter
- long non coding rna
- big data
- rectal cancer
- protein kinase
- case control
- patient reported
- functional connectivity