Galectins are a family of β-galactoside-binding
lectins that exert diverse extracellular and intracellular effects. Galectin-7 and
galectin-1 show opposing effects on proliferation and survival in different cell types. Galectin-7 is a p53-induced gene and an enhancer of apoptosis, whereas
galectin-1 induces tumorigenicity and resistance to apoptosis in several types of
cancers. We show here that in cells derived from
neurofibromin-deficient (Nf1(-/-))
malignant peripheral nerve sheath tumors (MPNSTs), Ras inhibition by
S-trans,trans-farnesylthiosalicylic-acid (FTS;
Salirasib) shifts the pattern of
galectin expression. Whereas FTS decreased levels of both active Ras and
galectin-1 expression, it dramatically increased both the
mRNA and
protein expression levels of galectin-7. Galectin-7 accumulation was mediated through JNK inhibition presumably resulting from the observed induction of p53, and was negatively regulated by the
AP-1 inhibitor JDP2. Expression of galectin-7 by itself decreased Ras activation in ST88-14 cells and rendered them sensitive to apoptosis. This observed shift in
galectin expression pattern together with the accompanying shift from cell proliferation to apoptosis represents a novel pattern of Ras inhibition by FTS. This seems likely to be an important phenomenon in view of the fact that both enhanced cell proliferation and defects of apoptosis constitute major hallmarks of human
cancers and play a central role in the resistance of MPNSTs to anti-
cancer treatments. These findings suggest that FTS, alone or in combination with
chemotherapy agents, may be worth developing as a possible treatment for MPNSTs.