ABCB1 inhibition provides a novel therapeutic target to block TWIST1-induced migration in medulloblastoma.

ABSTRACT:

Background

Therapeutic intervention in metastatic medulloblastoma is dependent on elucidating the underlying metastatic mechanism. We investigated whether an epithelial-mesenchymal transition (EMT)-like pathway could drive medulloblastoma metastasis.

Methods

A 3D Basement Membrane Extract (3D-BME) model was used to investigate medulloblastoma cell migration. Cell line growth was quantified with AlamarBlue metabolic assays and the morphology assessed by time-lapse imaging. Gene expression was analyzed by qRT-PCR and protein expression by immunohistochemistry of patient tissue microarrays and mouse orthotopic xenografts. Chromatin immunoprecipitation was used to determine whether the EMT transcription factor TWIST1 bound to the promoter of the multidrug pump ABCB1. TWIS

SUBMITTER: Nasir A 

PROVIDER: S-EPMC8080134 | biostudies-literature | 2021 Jan-Dec

REPOSITORIES: biostudies-literature