TIGP (BIO)—Sweet Poison: How Sugar Initiates Tumorigenesis in Pancreatic Cells

Abstract

Excess sugar's impact on obesity and diabetes is well known. However, an area that may surprise many people is consuming excessive amounts of sugar can contribute to an increased risk of pancreatic ductal adenocarcinoma (PDAC). However, a less well-known fact is whether consuming excessive amounts of sugar directly contributes to this risk. Our previous research has established a mechanistic link between disturbed glucose metabolism and genomic instability, which can induce oncogenic KRAS mutations and cell transformation, particularly in pancreatic cells. Recent experiments conducted on mice have confirmed that excess sugar in daily drinks can lead to increased DNA damage and potentially initiate cancer in pancreatic tissue. The effect of high sugar on pancreatic tissue may be due to the intrinsic ratio of GFAT and PFK activity, which limits UDP-GlcNAc levels. Moreover, GlcNAc induces DNA damage in all six organs examined, and inhibiting O-GlcNAcylation or supplementing the dNTP pool can reduce the induced DNA damage in these organs. These findings indicate that the mechanism of action is similar to that of high glucose treatment in pancreatic cells and suggest that sugar-rich beverages and high glucosamine uptake pose potential hazards to genomic stability and possibly cancer initiation.

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