期刊
ARTIFICIAL CELLS NANOMEDICINE AND BIOTECHNOLOGY
卷 46, 期 -, 页码 87-95出版社
TAYLOR & FRANCIS LTD
DOI: 10.1080/21691401.2018.1452022
关键词
MerTK; self-renewal; KRAS; STAT3; SRC
资金
- National Research Foundation (NRF)
- Ministry of Science, ICT and Future Planning, Korean Government [NRF-2015M2A2A7A01044998, NRF-2016R1C1B2010851]
- National Research Foundation of Korea [2015M2A2A7A01044998] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Receptor tyrosine kinase Mer (MerTK) has been shown to be highly expressed in Glioblastoma multiforme (GBM) in comparison to its healthy counterpart and is implicated in brain tumorigenesis. Clarifying the underlying mechanism of MerTK induced invasiveness would result in novel strategies to improve patient's response to chemotherapeutics. In vitro and in vivo assays were performed to examine the functional role of cancer stem sell (CSC) maintenance in MerTK associated invasiveness. In this article, we demonstrate that apart from GBM cells, MerTK is also upregulated in GBM stem-like cells and associated with an increased infiltrative potential of brain tumors in vivo. Silencing of MerTK suppressed the self-renewal of patient-derived GBM stem-like cells. The signaling mechanisms by which MerTK contributes to CSC maintenance have largely been obscure. Molecular analyses revealed that high expression of the signal transducer and activator of transcription 3 (STAT3)- Kirsten rat sarcoma viral oncogene homolog (KRAS) and proto-oncogene tyrosine-protein kinase SRC axis supports MerTK-induced CSC maintenance in GBM spheroids. Furthermore, a short-hairpin RNA-mediated MerTK knockdown effectively blocked invasiveness and N-cadherin expression in mouse xenografts. Collectively, our results uncover a critical function of MerTK in CSC maintenance. Considering the low basal level of MerTK expression in healthy brain cells, evaluation of MerTK as a therapeutic target should advance the research into better therapeutics for GBM.
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