Inhibition of the up-regulated
telomerase activity in
cancer cells has previously been shown to slow cell growth but only after prior telomere shortening. Previously, we have reported that, unexpectedly, a hairpin
short interfering RNA specifically targeting human
telomerase RNA rapidly inhibits the growth of human
cancer cells independently of p53 or telomere length and without bulk telomere shortening (Li, S., Rosenberg, J. E., Donjacour, A. A., Botchkina, I. L., Hom, Y. K., Cunha, G. R., and Blackburn, E. H. (2004)
Cancer Res. 64, 4833-4840). Here we have demonstrated that such
telomerase RNA knockdown in
cancer cells does not cause telomere uncapping but rather induces changes in the global gene expression profile indicative of a novel response pathway, which includes suppression of specific genes implicated in angiogenesis and
metastasis, and is distinct from the expression profile changes induced by telomere-uncapping mutant template
telomerase RNAs. These cellular responses to depleting
telomerase in human
cancer cells together suggest that
cancer cells are "
telomerase-addicted" and uncover functions of
telomerase in
tumor growth and progression in addition to telomere maintenance.