Knocking Down Galectin 1 in Human Hs683 Glioblastoma Cells Impairs Both Angiogenesis and Endoplasmic Reticulum Stress Responses
Le Mercier M, Mathieu V, Haibe-Kains B, Bontempi G, Mijatovic T, Decaestecker C; Kiss R and Lefranc F
Galectin
(Gal) 1 is a hypoxia-regulated proangiogenic factor that also directly
participates in glioblastoma cell migration. To determine how Gal-1
exerts its proangiogenic effects, we investigated Gal-1 signaling in
the human Hs683 glioblastoma cell line. Galectin 1 signals through the
endoplasmic reticulum transmembrane kinase/ribonuclease
inositol-requiring 1[alpha], which regulates the expression of
oxygen-regulated protein 150. Oxygen-regulated protein 150 controls
vascular endothelial growth factor maturation. Galectin 1 also
modulates the expression of 7 other hypoxia-related genes (i.e. CTGF,
ATF3, PPP1R15A, HSPA5, TRA1, and CYR61) that are implicated in
angiogenesis. Decreasing Gal-1 expression in Hs683 orthotopic
xenografts in mouse brains by siRNA administration impaired endoplasmic
reticulum stress and enhanced the therapeutic benefits of the
proautophagic drug temozolomide. These results suggest that decreasing
Gal-1 expression (e.g. through brain delivery of nonviral infusions of
anti-Gal-1 siRNA in patients) can represent an additional therapeutic
strategy for glioblastoma.