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Abstract: This thesis
describes functions of the cell surface adhesion molecule Nectin-like molecule 5
(Necl-5) and its role in the pathogenesis of the deadly brain tumor glioblastoma (GBM).
This thesis presents data showing that Necl-5 has two functions that have not been
previously described. First, it promotes MMP-2 production, which is important for the
invasive phenotype of GBM, and that ... read moreMMP-2 production correlates with Necl-5 dependent
Akt activation. Akt is known to promote MMP-2 expression in GBM, but this is the first
link between Necl-5, Akt, and MMP-2 to be described. Second, Necl-5 protects GBM cells
from receptor-mediated apoptosis, but not from chemotherapy-induced apoptosis.
Furthermore, Necl-5 participates with CD44 to afford GBM cells this protection. It was
previously shown that CD44 binds Necl-5, but the relevance of this interaction was
heretofore unknown. As these processes are central to GBM pathogenesis, they support the
idea that inhibition of Necl-5 function could inhibit tumor growth and
survival.
Thesis (Ph.D.)--Tufts University,
2011.
Submitted to the Dept. of Cellular &
Molecular Physiology.
Advisor: Daniel
Jay.
Committee: Brent Cochran, and Ira
Herman.
Keyword:
Physiology.read less
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