Abstract
Pancreatic cancer is characterized by an often dramatic outcome (five year survival < 5%) related to a late diagnosis and a lack of efficient therapy. Therefore, clinicians desperately need new biomarkers and new therapeutic tools to develop new efficient therapies. Mucins belong to an ever increasing family of O-glycoproteins. Secreted mucins are the main component of mucus protecting the epithelia whereas membrane-bound mucins are thought to play important biological roles in cell-cell and cell-matrix interactions, in cell signaling and in modulating biological properties of cancer cells. In this review, we will focus on the altered expression pattern of mucins in pancreatic cancer, from the early neoplastic lesion Pancreatic Intraepithelial Neoplasia (PanIN) to invasive pancreatic carcinomas, and the molecular mechanisms (including genetic and epigenetic regulation) and signaling pathways known to control their expression. Moreover, we will discuss the recent advances about the biology of both secreted and membrane-bound mucins and their key roles in pancreatic carcinogenesis and resistance to therapy. Finally, we will discuss exciting opportunities that mucins offer as potential therapeutic targets in pancreatic cancer.
Highlights
Pancreatic CancerPancreatic Ductal Adenocarcinoma (PDAC) is the fourth leading cause of death by cancer in the world
Pancreatic cancer is characterized by an often dramatic outcome related to a late diagnosis and a lack of efficient therapy
Numerous reports have shown that the cytoplasmic tail of MUC1 which contains a SH2 interaction domain and several kinase phosphorylation sites, acts as a docking protein for cell signaling involving notably -catenin, c-Src, glycogen-synthase kinase-3β (GSK-3β), protein kinase Cδ (PKCδ), and the four members of the ErbB receptor family
Summary
Pancreatic Ductal Adenocarcinoma (PDAC) is the fourth leading cause of death by cancer in the world. Pathological and genetics studies have identified three different preneoplastic lesions of the duct as precursors of pancreatic ductal adenocarcinoma (PDAC) [5,6] These lesions are pancreatic intraepithelial neoplasia (PanIN), intraductal papillary mucinous neoplasm (IPMN) and mucinous cystic neoplasm (MCN). MCN have a good prognosis since the five year survival is close to 100% for patients who undergo surgical resection without invasive carcinoma. Surgery is the only treatment modality with the potential to cure, but it is only likely to be effective in patients without diffuse metastatic disease [7] These disastrous statistics for pancreatic cancer show that it is urgent to develop new diagnostic and/or prognostic tools for the clinicians in order to propose better healthcare management of the disease.
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