Tumor-treating fields induce autophagy by blocking the Akt2/miR29b axis in glioblastoma cells

Oncogene
Eun Ho KimSang-Gu Hwang

Abstract

Tumor-treating fields (TTFs) - a type of electromagnetic field-based therapy using low-intensity electrical fields - has recently been characterized as a potential anticancer therapy for glioblastoma multiforme (GBM). However, the molecular mechanisms involved remain poorly understood. Our results show that the activation of autophagy contributes to the TTF-induced anti-GBM activity in vitro or in vivo and GBM patient stem cells or primary in vivo culture systems. TTF-treatment upregulated several autophagy-related genes (~2-fold) and induced cytomorphological changes. TTF-induced autophagy in GBM was associated with decreased Akt2 expression, not Akt1 or Akt3, via the mTOR/p70S6K pathway. An Affymetrix GeneChip miRNA 4.0 Array analysis revealed that TTFs altered the expression of many microRNAs (miRNAs). TTF-induced autophagy upregulated miR-29b, which subsequently suppressed the Akt signaling pathway. A luciferase reporter assay confirmed that TTFs induced miR-29b to target Akt2, negatively affecting Akt2 expression thereby triggering autophagy. TTF-induced autophagy suppressed tumor growth in GBM mouse models subjected to TTFs as determined by positron emission tomography and computed tomography (PET-CT). GBM patient stem ce...Continue Reading

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Citations

Sep 18, 2020·Technology in Cancer Research & Treatment·Ju Yeon OhEun Ho Kim
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Methods Mentioned

BETA
xenografts
flow cytometry
transmission electron microscopy
co-immunoprecipitation
co-immunoprecipitation assay
FACS
transfection
ELISA
xenograft
fluorescence-activated cell sorting

Software Mentioned

DIANA
ONCOMINE
ASSESS
microT

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