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dc.contributor.authorDai, Cathleen
dc.date.accessioned2019-11-28T16:10:09Z
dc.date.available2019-11-28T16:10:09Z
dc.identifier.urihttp://hdl.handle.net/10222/76691
dc.description.abstractCurrently, there is interest in targeting cancer stem cells (CSCs) for cancer therapy. CSCs are characterized by self-renewal and the potential to differentiate into various tumor cell types. One therapeutic strategy is to modulate cancer metabolism, in which NAD+ is a central molecule. NAPRT is one of the major NAD+-synthesizing enzymes, and we studied its role in three models of cancer stem-like cells (CSLCs). We show that CSLCs highly express NAPRT. Knockdown of NAPRT in CSLCs inhibits cell proliferation and stemness features, and promotes differentiation, senescence, or cell death. We observed that NAD+-dependent SIRT7 was consistently downregulated in cancer cells with shNAPRT, a significant correlation between NAPRT and SIRT7 expression is evident in cancer patient datasets, and knockdown of SIRT7 induces a proteomic profile similar to that of shNAPRT cells. We therefore propose that SIRT7 is involved in shNAPRT antitumor effects. Together, these findings put forward novel therapeutic implications for NAPRT-SIRT7 axis in cancer therapy.en_US
dc.language.isoenen_US
dc.subjectcanceren_US
dc.subjectNAPRTen_US
dc.subjectcancer stem cellen_US
dc.titleINVESTIGATING THE ROLE OF NICOTINIC ACID PHOSPHORIBOSYL TRANSFERASE IN CANCERen_US
dc.date.defence2018-07-03
dc.contributor.departmentDepartment of Microbiology & Immunologyen_US
dc.contributor.degreeMaster of Scienceen_US
dc.contributor.external-examinerDr. Melanie Coombsen_US
dc.contributor.graduate-coordinatorDr. Brent Johnstonen_US
dc.contributor.thesis-readerDr. Christopher Richardsonen_US
dc.contributor.thesis-readerDr. David Waismanen_US
dc.contributor.thesis-readerDr. Paola Marcatoen_US
dc.contributor.thesis-supervisorDr. Shashi Gujaren_US
dc.contributor.ethics-approvalReceiveden_US
dc.contributor.manuscriptsYesen_US
dc.contributor.copyright-releaseYesen_US
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