TY - JOUR
T1 - Mucins and Wnt/β-catenin signaling in gastrointestinal cancers
T2 - An unholy nexus
AU - Pai, Priya
AU - Rachagani, Satyanarayana
AU - Dhawan, Punita
AU - Batra, Surinder K.
N1 - Funding Information:
National Institutes of Health, NIH (EDRN UO1 CA111294, SPORE P50 CA127297, TMEN U54 CA163120 and RO1 CA183459).
Publisher Copyright:
© The Author 2016.
PY - 2015/10/17
Y1 - 2015/10/17
N2 - The Wnt/β-catenin signaling pathway is indispensable for embryonic development, maintenance of adult tissue homeostasis and repair of epithelial injury. Unsurprisingly, aberrations in this pathway occur frequently in many cancers and often result in increased nuclear β-catenin. While mutations in key pathway members, such as β-catenin and adenomatous polyposis coli, are early and frequent occurrences in most colorectal cancers (CRC), mutations in canonical pathway members are rare in pancreatic ductal adenocarcinoma (PDAC). Instead, in the majority of PDACs, indirect mechanisms such as promoter methylation, increased ligand secretion and decreased pathway inhibitor secretion work in concert to promote aberrant cytosolic/nuclear localization of β-catenin. Concomitant with alterations in β-catenin localization, changes in mucin expression and localization have been documented in multiple malignancies. Indeed, numerous studies over the years suggest an intricate and mutually regulatory relationship between mucins (MUCs) and β-catenin. In the current review, we summarize several studies that describe the relationship between mucins and β-catenin in gastrointestinal malignancies, with particular emphasis upon colorectal and pancreatic cancer.
AB - The Wnt/β-catenin signaling pathway is indispensable for embryonic development, maintenance of adult tissue homeostasis and repair of epithelial injury. Unsurprisingly, aberrations in this pathway occur frequently in many cancers and often result in increased nuclear β-catenin. While mutations in key pathway members, such as β-catenin and adenomatous polyposis coli, are early and frequent occurrences in most colorectal cancers (CRC), mutations in canonical pathway members are rare in pancreatic ductal adenocarcinoma (PDAC). Instead, in the majority of PDACs, indirect mechanisms such as promoter methylation, increased ligand secretion and decreased pathway inhibitor secretion work in concert to promote aberrant cytosolic/nuclear localization of β-catenin. Concomitant with alterations in β-catenin localization, changes in mucin expression and localization have been documented in multiple malignancies. Indeed, numerous studies over the years suggest an intricate and mutually regulatory relationship between mucins (MUCs) and β-catenin. In the current review, we summarize several studies that describe the relationship between mucins and β-catenin in gastrointestinal malignancies, with particular emphasis upon colorectal and pancreatic cancer.
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U2 - 10.1093/carcin/bgw005
DO - 10.1093/carcin/bgw005
M3 - Review article
C2 - 26762229
AN - SCOPUS:84959916573
VL - 37
SP - 223
EP - 232
JO - Carcinogenesis
JF - Carcinogenesis
SN - 0143-3334
IS - 3
ER -