Telomerase is a cellular ribonucleoprotein reverse transcriptase that plays a 
crucial role in telomere maintenance. This enzyme is expressed in approximately 
90% of human tumors, but not in the majority of normal somatic cells. imetelstat 
sodium (GRN163L), is a 13-mer oligonucleotide N3'→P5' thio-phosphoramidate lipid 
conjugate, which represents the latest generation of telomerase inhibitors 
targeting the template region of the human functional telomerase RNA (hTR) 
subunit. In preclinical trials, this compound has been found to inhibit 
telomerase activity in multiple cancer cell lines, as well as in vivo xenograft 
mouse models. Currently, GRN163L is being investigated in several clinical 
trials, including a phase II human non‑small cell lung cancer clinical trial, in 
a maintenance setting following standard doublet chemotherapy. In addition to 
the inhibition of telomerase activity in cancer cell lines, GRN163L causes 
morphological cell rounding changes, independent of hTR expression or telomere 
length. This leads to the loss of cell adhesion properties; however, the 
mechanism underlying this effect is not yet fully understood. In the present 
study, we observed that GRN163L treatment leads to the loss of adhesion in A549 
lung cancer cells, due to decreased E-cadherin expression, leading to the 
disruption of the cytoskeleton through the alteration of actin, tubulin and 
intermediate filament organization. Consequently, the less adherent cancer cells 
initially cease to proliferate and are arrested in the G1 phase of the cell 
cycle, accompanied by decreased matrix metalloproteinase-2 (MMP-2) expression. 
These effects of GRN163L are independent of its telomerase catalytic activity 
and may increase the therapeutic efficacy of GRN163L by decreasing the adhesion, 
proliferation and metastatic potential of cancer cells in vivo.