Abstract
Colorectal cancer (CRC) is the fourth leading cause of cancer-related deaths in the world. Drug resistance of tumour cells remains the main challenge toward curative treatments efficiency. Several epidemiologic studies link emergence and recurrence of this cancer to metabolic disorders. Glycosylation that modifies more than 80% of human proteins is one of the most widepread nutrient-sensitive post-translational modifications. Aberrant glycosylation participates in the development and progression of cancer. Thus, some of these glycan changes like carbohydrate antigen CA 19-9 (sialyl Lewis a, sLea) or those found on carcinoembryonic antigen (CEA) are already used as clinical biomarkers to detect and monitor CRC. The current review highlights emerging evidences accumulated mainly during the last decade that establish the role played by altered glycosylations in CRC drug resistance mechanisms that induce resistance to apoptosis and activation of signaling pathways, alter drug absorption and metabolism, and led to stemness acquisition. Knowledge in this field of investigation could aid to the development of better therapeutic approaches with new predictive biomarkers and targets tied in with adapted diet.
Highlights
According to the World Health Organization (WHO) [1], colorectal cancer (CRC) is the third most common diagnosed cancer and the fourth cause of cancer-related death in the world (1,3 million new cases and 694 000 deaths respectively in 2012)
While the percentages of obese and diabetic individuals are progressing rapidly in industrialized countries, epidemiological data show these patients display an increased risk of colorectal cancer (CRC) [176] and relapse after chemotherapy treatment [177,178,179]. These disorders may increase the availability of precursors involved in the biosynthesis of the nucleotide www.impactjournals.com/oncotarget sugar donor uridine-5’-diphosphate-N-acetylglucosamine (UDP-GlcNAc) through the hexosamine biosynthetic pathway (HBP) and deregulate glycosylation processes
Glycosylation is a wide group of post-translational modifications and aberrant protein glycosylation is a common feature associated with cancer status and progression [27]
Summary
According to the World Health Organization (WHO) [1], colorectal cancer (CRC) is the third most common diagnosed cancer and the fourth cause of cancer-related death in the world (1,3 million new cases and 694 000 deaths respectively in 2012). Ni et al showed that β3GnT-8 overexpression and silencing respectively increases and decreases levels of HG-CD147 in LoVo metastatic colon cancer cell line revealing that HG-CD147 glycans consists of β1,6-branched poly-LacNAc chains [51]. Overexpression of ST6GalT-1 and α2,6-sialylation of β1 integrins prevents galectin-3 (Gal-3) binding and pro-apoptotic activity in SW48 colon cancer cells (Figure 4C).
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