Blockade of EGFR signaling promotes glioma stem-like cell invasiveness by abolishing ID3-mediated inhibition of p27 and MMP3 expression |
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| Authors: | Xun Jin Xiong Jin Young-Woo Sohn Jinlong Yin Sung-Hak Kim Kaushal Joshi Do-Hyun Nam Ichiro Nakano Hyunggee Kim |
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| Affiliation: | 1. School of Life Sciences and Biotechnology, Korea University, Seoul 136-713, Republic of Korea;2. Specific Organs Cancer Branch, Research Institute and Hospital, National Cancer Center, Goyang, Gyeonggi 310-769, Republic of Korea;3. Department of Neurosurgery, Samsung Medical Center and Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Seoul 135-710, Republic of Korea;4. Department of Neurological Surgery, James Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA |
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| Abstract: | Aberrant epidermal growth factor receptor (EGFR) signaling is a typical oncogenic signature in glioblastoma. Here, we show that EGFR inhibition in primary glioma stem cells (GSCs) with oncogenic EGFRvIII and EGFRvIII-transduced glioma stem-like cells promotes invasion by decreasing ID3 levels. ID3 suppresses GSC invasiveness by inhibiting p27KIP1-RhoA-dependent migration and MMP3 expression. Xenograft and human glioblastoma specimens show that ID3 localizes within glioblastoma cores, whereas p27KIP1 and MMP3 are predominantly expressed in glioma cells in invasive fronts. Together, our findings show that EGFR inhibition induces GSC invasiveness by abolishing ID3-mediated inhibition of p27KIP1 and MMP3 expression. |
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| Keywords: | Glioma stem cells Glioblastoma EGFR ID3 Invasion |
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