Journal
CANCER LETTERS
Volume 328, Issue 2, Pages 235-242Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2012.09.005
Keywords
Glioma stem cells; Glioblastoma; EGFR; ID3; Invasion
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Funding
- National R&D Program for Cancer Control, Ministry of Health and Welfare, Republic of Korea [1020270]
- American Cancer Society [MRSG-08-108-01]
- NIH/NCI [1R21CA135013-01A1]
- Brain Korea 21 project
- MEST
- Korea Health Promotion Institute [1020270] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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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 p27(KIP1)-RhoA-dependent migration and MMP3 expression. Xenograft and human glioblastoma specimens show that ID3 localizes within glioblastoma cores, whereas p27(KIP1) 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 p27(KIP1) and MMP3 expression. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
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