title: Blockade of EGFR signaling promotes glioma stem-like cell invasiveness by abolishing ID3-mediated inhibition of p27(KIP1) and MMP3 expression.
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 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.
authors.affiliation: School of Life Sciences and Biotechnology, Korea University, Seoul 136-713, Republic of Korea.
authors.forename: Xun
authors.initials: X
authors.lastname: Jin
authors.forename: Xiong
authors.initials: X
authors.lastname: Jin
authors.forename: Young-Woo
authors.initials: YW
authors.lastname: Sohn
authors.forename: Jinlong
authors.initials: J
authors.lastname: Yin
authors.forename: Sung-Hak
authors.initials: SH
authors.lastname: Kim
authors.forename: Kaushal
authors.initials: K
authors.lastname: Joshi
authors.forename: Do-Hyun
authors.initials: DH
authors.lastname: Nam
authors.forename: Ichiro
authors.initials: I
authors.lastname: Nakano
authors.forename: Hyunggee
authors.initials: H
authors.lastname: Kim
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D005910:Glioma / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051796:Inhibitor of Differentiation Proteins / Q000235:genetics / Q000378:metabolism*; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism*; D051379:Mice; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D011799:Quinazolines / Q000494:pharmacology / Q000633:toxicity; D015398:Signal Transduction / Q000187:drug effects; D020032:Tyrphostins / Q000494:pharmacology / Q000633:toxicity
chemical_list: D051796:Inhibitor of Differentiation Proteins; D009363:Neoplasm Proteins; D011799:Quinazolines; D020032:Tyrphostins; C410723:epidermal growth factor receptor VIII; D050760:Cyclin-Dependent Kinase Inhibitor p27; C075640:ID3 protein, human; C101044:RTKI cpd; D066246:ErbB Receptors; D019278:Matrix Metalloproteinase 3