Glycosylation: A possible link between diet and stemness in intestinal cancer

• Applicant: Privatdozentin Melek Canan Arkan, Ph.D.
• Subject Area: Gastroenterology
• Term: from 2017 to 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 385542443

Current knowledge still lacks cause and effect of key processes that take place during malignant transformation in colorectal cancer (CRC). These are important not only for understanding the disease pathology in the intestine but also for designing realistic strategies to limit the mortality that it causes.Tumor cells display a wide range of glycosylation changes compared to non transformed tissue. Indeed, modifications in the glycosylation pattern appear as a hallmark of cancer. Glycosylation, the most commonly occurring posttranslational modification (PTM), plays a critical role in intercellular and intracellular processes that are fundamental to the development of multicellularity. In fact, PTMs are considered a dominant signature of pluripotency and stemness. A recent study suggests high fat diet (HFD) induced obesity augments the numbers and function of Lgr5+ intestinal stem cells and increases their capacity to initiate tumors in the intestine thus adding another layer of complexity over dietary cues in regulating intestinal tumor biology. Our current understanding of the controlling mechanisms that set the balance between stem cell self renewal and differentiation is extensively derived from genomic, transcriptomic, and epigenomic studies, and often undermines the functional significance of glycan chains, despite their high abundance in stem cell niche. An intricate association between glycosylation and stemness stands solid, although whether this would be a potential link between diet and cancer remains to be clarified. This proposal aims at unraveling whether glycan structure modifications are functionally involved in inducing tumor cell stemness during diet associated cancer. Given the ever increasing worldwide incidence of diet linked malignancies, defining a role for glycans during dedifferentiation in CRC is timely. Since glycosylation is a reversible modification and highly susceptible to environmental factors, characterizing glycans under a diet context can set the stage for early detection biomarkers and future drug discovery aimed at developing therapeutic interventions against intestinal cancer.

• DFG Programme: Research Grants