INVESTIGATING THE ROLE OF NICOTINIC ACID PHOSPHORIBOSYL TRANSFERASE IN CANCER

Abstract

Currently, 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.