MUC13 contributes to rewiring of glucose metabolism in pancreatic cancer

Oncogenesis
Sonam KumariM Jaggi

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 correlati...Continue Reading

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Citations

Oct 2, 2019·Cancers·Liang YanHaoqiang Ying
Dec 11, 2019·British Journal of Cancer·Sonam KumariMeena Jaggi
Jan 25, 2019·Journal of Experimental & Clinical Cancer Research : CR·Vivek K KashyapSubhash C Chauhan
Nov 26, 2020·International Journal of Molecular Sciences·Justin F CreedenRobert E McCullumsmith
Nov 18, 2020·International Journal of Molecular Sciences·Vikrant Rai, Swati Agrawal
Apr 5, 2021·Cancer Metastasis Reviews·Saravanakumar MarimuthuMoorthy P Ponnusamy
Mar 30, 2021·Clinica Chimica Acta; International Journal of Clinical Chemistry·Ang LiYanfang Jiang

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Methods Mentioned

BETA
surgical resection
PCR
nuclear translocation
ubiquitination
co-immunoprecipitation
proximity ligation assay
co-IP
co-immunoprecipitation assay
confocal microscopy

Software Mentioned

excel
PLA
Zen

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