Pancreatic Cancer: Pursuit of Mucins from Progression to Prognosis

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy characterized by a late diagnosis, poor survival, and limited treatment options. Over the past two decades, extensive studies have illuminated mucin deregulation as an essential hallmark in PDAC. Mucins are large molecular weight glycoproteins with characteristic O-linked and N-linked oligosaccharides (glycans) and distinct domains. Mucin overexpression and aberrant glycosylation contribute to disease pathobiology through intricate interactions with extracellular matrix (ECM) and stromal components. Moreover, recent studies are evaluating the utility of mucins or their associated glycans as diagnostic and prognostic markers in a clinical setting for PDAC patients. This chapter elaborates our understanding of how mucins pursue the transformation of a healthy epithelial cell to full-blown PDAC by altering phenotypic characteristics of the cancer cell for invasion and migration, stabilizing growth factor receptors or receptor tyrosine kinases (RTKs) and allowing constitutive signaling for tumorigenesis and metastasis and influencing interactions with ECM and stroma thereby remodeling TME. Cumulatively, these phenomena elicit disease with a suppressive immune milieu and the malignant phenotype. We further compile studies elaborating their diagnostic and prognostic implications. Overall, this comprehensive information should lend an understanding of mucins’ convolutions in worsening disease outcomes and report novel mucin-based biomarkers in PDAC.