Epidermal growth factor induces matrix metalloproteinase-1 (MMP-1) expression and invasion in glioma cell lines via the MAPK pathway

M. Anand, T. Van Meter, Helen Fillmore

Research output: Contribution to journalArticlepeer-review


Glioblastoma multiforme (GBM) is an aggressive cancer with a poor survival rate. A key component that contributes to the poor prognosis is the capacity of glioma cells to invade local brain tissue in a diffuse manner. Among various proteases that aid in the process of invasion, matrix metalloproteinase-1 (MMP-1) has been identified as an important contributory factor in various cancers. Apart from its traditional role in cleaving its primary extracellular matrix (ECM) substrates, and like other members of the matrix metalloproteinase family, MMP-1 can activate latent forms of bio-active molecules initiating downstream pro-invasive and pro-oncogenic signaling mechanisms. MMP-1 expression is regulated by several growth factors including epidermal growth factor (EGF). Due to the fact that the epidermal growth factor receptor (EGFR) is aberrantly overexpressed in GBM, we wanted to examine in greater detail the signaling mechanisms by which MMP-1 expression and invasion is driven by EGF in GBM cells. T98G cells treated with EGF resulted in an induction of MMP-1 expression following EGFR activation. Inhibition of EGFR by both pharmacologic and genetic approaches abrogated this induction. Repression of the mitogen activated protein kinase (MAPK) signaling led to the inhibition of EGF-induced MMP-1 whereas the PI3-kinase/AKT signaling was not associated with EGFR-mediated MMP-1 induction. Inhibition of EGFR signaling also led to a decrease in T98G invasion. These data suggest that EGFR mediated MMP-1 regulation is mainly via the MAPK pathway in T98G cells and inhibition of EGFR and MMP-1 results in a decrease in T98G cell invasion.
Original languageEnglish
Pages (from-to)679-687
Number of pages9
JournalJournal of Neuro-Oncology
Issue number3
Publication statusPublished - 2011


Dive into the research topics of 'Epidermal growth factor induces matrix metalloproteinase-1 (MMP-1) expression and invasion in glioma cell lines via the MAPK pathway'. Together they form a unique fingerprint.

Cite this