Cancers, Vol. 11, Pages 1635: SLUG Directs the Precursor State of Human Brain Tumor Stem Cells

Cancers, Vol. 11, Pages 1635: SLUG Directs the Precursor State of Human Brain Tumor Stem Cells Cancers doi: 10.3390/cancers11111635 Authors: Charles Chesnelong Xiaoguang Hao Orsolya Cseh Alice Yijun Wang H. Artee Luchman Samuel Weiss In glioblastoma (GBM), brain tumor stem cells (BTSCs) encompass heterogenous populations of multipotent, self-renewing, and tumorigenic cells, which have been proposed to be at the root of therapeutic resistance and recurrence. While the functional significance of BTSC heterogeneity remains to be fully determined, we previously distinguished relatively quiescent stem-like precursor state from the more aggressive progenitor-like precursor state. In the present study, we hypothesized that progenitor-like BTSCs arise from stem-like precursors through a mesenchymal transition and drive post-treatment recurrence. We first demonstrate that progenitor-like BTSCs display a more mesenchymal transcriptomic profile. Moreover, we show that both mesenchymal GBMs and progenitor-like BTSCs are characterized by over-activated STAT3/EMT pathways and that SLUG is the primary epithelial to mesenchymal transition (EMT) transcription factor directly regulated by STAT3 in BTSCs. SLUG overexpression in BTSCs enhances invasiveness, promotes inflammation, and shortens survival. Importantly, SLUG overexpression in a quiescent stem-like BTSC line enhances tumorigenesis. Finally, we report that recurrence is associated with SLUG-induced transcriptional cha...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research