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dc.contributor.authorMENDER, ILGEN
dc.contributor.authorSENTURK, SERIF
dc.contributor.authorOZGUNES, NURIMAN
dc.contributor.authorAKCALI, K. CAN
dc.contributor.authorKLETSAS, DIMITRIS
dc.contributor.authorGRYAZNOV, SERGEI
dc.contributor.authorCAN, ALP
dc.contributor.authorSHAY, JERRY W.
dc.contributor.authorDIKMEN, Z. GUNNUR
dc.date.accessioned2019-12-12T06:24:56Z
dc.date.available2019-12-12T06:24:56Z
dc.date.issued2013
dc.identifier.issn1019-6439
dc.identifier.urihttps://doi.org/10.3892/ijo.2013.1865
dc.identifier.urihttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4738197/
dc.identifier.urihttp://hdl.handle.net/11655/16222
dc.description.abstractTelomerase 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.
dc.language.isoen
dc.relation.isversionof10.3892/ijo.2013.1865
dc.rightsinfo:eu-repo/semantics/openAccess
dc.titleImetelstat (A Telomerase Antagonist) Exerts Off-Target Effects On The Cytoskeleton
dc.typeinfo:eu-repo/semantics/article
dc.typeinfo:eu-repo/semantics/publishedVersion
dc.relation.journalInternational Journal of Oncology
dc.contributor.departmentTıbbi Biyokimya
dc.identifier.volume42
dc.identifier.issue5
dc.identifier.startpage1709
dc.identifier.endpage1715
dc.description.indexPubMed
dc.description.indexWoS
dc.description.indexScopus


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