Aberrant glycosylation and cancer biomarker discovery: a promising and thorny journey

Abstract

Glycosylation is among the most important post-translational modifications for proteins and is of intrinsic complex character compared with DNAs and naked proteins. Indeed, over 50%–70% of proteins in circulation are glycosylated, and the “sweet attachments” have versatile structural and functional implications. Both the configuration and composition of the attached glycans affect the biological activities of consensus proteins significantly. Glycosylation is generated by complex biosynthetic pathways comprising hundreds of glycosyltransferases, glycosidases, transcriptional factors, transporters and the protein backbone. In addition, lack of direct genetic templates and glyco-specific antibodies such as those commonly used in DNA amplification and protein capture makes research on glycans and glycoproteins even more difficult, thus resulting in sparse knowledge on the pathophysiological implications of glycosylation. Fortunately, cutting-edge technologies have afforded new opportunities and approaches for investigating cancer-related glycosylation. Thus, glycans as well as aberrantly glycosylated protein-based cancer biomarkers have been increasingly recognized. This mini-review highlights the most recent developments in glyco-biomarker studies in an effort to discover clinically relevant cancer biomarkers using advanced analytical methodologies such as mass spectrometry, high-performance liquid chromatographic/ultra-performance liquid chromatography, capillary electrophoresis, and lectin-based technologies. Recent clinical-centered glycobiological studies focused on determining the regulatory mechanisms and the relation with diagnostics, prognostics and even therapeutics are also summarized. These studies indicate that glycomics is a treasure waiting to be mined where the growth of cancer-related glycomics and glycoproteomics is the next great challenge after genomics and proteomics.

Differential O- and Glycosphingolipid Glycosylation in Human Pancreatic Adenocarcinoma Cells With Opposite Morphology and Metastatic Behavior

“…The transcripts identified as differentially expressed were those with adjusted p < 0.1 and a difference in fold change > 1. 5 Quantitative Real-Time PCR mRNA was isolated from cells at 60% confluence using the mRNA Capture kit (Roche, Basel, Switzerland) according to the manufacturer's guidelines. cDNA was synthesized with Reverse Transcription System kit (Promega, San Luis Obispo, CA).…”

“…Glycosylation is one of the most common and complex posttranslational modifications of proteins, and glycans also occur conjugated to lipids (2). Changes in glycosylation are involved in the regulation of many cancer-related processes such as signaling, cell adhesion, tumor proliferation, invasion, metastasis, and angiogenesis (2)(3)(4)(5). Importantly, cancer-associated glycans also provide a set of diagnostic biomarkers and potential targets for therapeutic strategies (2,(5)(6)(7).…”

“…Changes in glycosylation are involved in the regulation of many cancer-related processes such as signaling, cell adhesion, tumor proliferation, invasion, metastasis, and angiogenesis (2)(3)(4)(5). Importantly, cancer-associated glycans also provide a set of diagnostic biomarkers and potential targets for therapeutic strategies (2,(5)(6)(7). For example, CA 19-9 which is an antigen carrying the glycan epitope sialyl Lewis A (sLe A ) is a widely used biomarker in clinical diagnosis of PDAC (4,8).…”

TSTA3 facilitates esophageal squamous cell carcinoma progression through regulating fucosylation of LAMP2 and ERBB2

“…Aberrant glycosylation has been recognized as a hallmark of cancer. Glycosylation is often involved in the folding, polymerization, maturation and transport of protein peptide chains, which plays an important role in the regulation of cellular functions 3 , 4 . Fucosylation is one of the most common glycosylation modification and many studies revealed that increased fucosylation contributed to many malignant transformation events, such as invasion, metastasis, angiogenesis and immune evasion 5 , 6 .…”

Oncogenic Signaling in Tumorigenesis and Applications of siRNA Nanotherapeutics in Breast Cancer

“…Triple-negative breast cancer (TNBC) defines the disease without or having less expression of the well-known breast cancer markers like ER, PR, and HER/neu [18], therefore, requiring different treatment approaches. Glycotherapy is one of the potential strategies to target aberrant glycosylation that promotes abnormal cellular activities and carcinogenesis [19]. The aspragine-linked (N-linked) glycoprotein was found to have roles in the progression of breast cancer, such as angiogenesis [20].…”