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onsdag 7 november 2018

MUC13 ( 3q21.2), DRCC, MUC-13

 https://www.ncbi.nlm.nih.gov/gene/56667
DRCC1; MUC-13
Summary
Epithelial mucins, such as MUC13, are a family of secreted and cell surface glycoproteins expressed by ductal and glandular epithelial tissues (Williams et al., 2001 [PubMed 11278439]).[supplied by OMIM, Jul 2008]
Expression
Biased expression in duodenum (RPKM 317.3), small intestine (RPKM 271.9) and 4 other tissues 
Protein:  Preferred Names
mucin-13
Names
down-regulated in colon cancer 1
mucin 13, epithelial transmembrane
https://www.ncbi.nlm.nih.gov/protein/NP_149038.3
 
2014:   https://www.ncbi.nlm.nih.gov/pubmed/25277192
 2015 :  https://www.ncbi.nlm.nih.gov/pubmed/25672256/

2018 Feb 22;7(2):19. doi: 10.1038/s41389-018-0031-0.
MUC13 contributes to rewiring of glucose metabolism in pancreatic cancer.
Abstract
Pancreatic tumors are rewired for high-glucose metabolism and typically present with exceptionally poor prognosis. Recently, we have shown that MUC13, which is highly expressed in pancreatic tumors, promotes tumor progression via modulation of HER2 receptor tyrosine kinase activity. Herein, we investigate a novel, MUC13-mediated molecular mechanism responsible for higher glucose metabolism in pancreatic tumors. Our results demonstrate that MUC13 expression leads to the activation/nuclear translocation of NF-κB p65 and phosphorylation of IκB, which in turn upregulates the expression of important proteins (Glut-1, c-Myc, and Bcl-2) that are involved in glucose metabolism. MUC13 functionally interacts and stabilizes Glut-1 to instigate downstream events responsible for higher glucose uptake in pancreatic cancer cells.

 Altered MUC13 expression by overexpression and knockdown techniques effectively modulated glucose uptake, lactate secretion, and metastatic phenotypes in pancreatic cancer cells. NF-κB inhibitor, Sulfasalazine, abrogates the MUC13 and Glut-1 interaction, and attenuates events associated with MUC13-induced glucose metabolism. Pancreatic ductal adenocarcinoma (PDAC) patient tissue samples also show a positive correlation between the expression of these two proteins. These results delineate how MUC13 rewire aberrant glucose metabolism to enhance aggressiveness of pancreatic cancer and revealed a novel mechanism to develop newer therapeutic strategies for this exceptionally difficult cancer.
PMID: 29467405
PMCID:PMC5833644
DOI:10.1038/s41389-018-0031-0

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