Journal
AGING-US
Volume 12, Issue 8, Pages 6808-6822Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/aging.103044
Keywords
proliferation; apoptosis; glycolysis; Wnt/beta-catenin; gemcitabine
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Funding
- Natural Science Foundation of Shanghai [17ZR1439300]
- Shanghai Municipal Health and Family Planning Commission Scientific Research Project [201640269]
- National Natural Science Foundation of China [81772955]
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Altered expression of family with sequence similarity 84, member B (FAM84B) has been found in various human cancers. However, the expression and function of FAM84B in pancreatic ductal adenocarcinoma (PDAC) has not been studied. Here, by analyzing The Cancer Genome Atlas cohort, we found that FAM84B amplification was observed in 11% of 141 PDAC patients, and FAM84B amplification was correlated with higher mRNA expression of FAM84B. FAM84B amplification and overexpression was significantly correlated with poor overall survival. Moreover, knockdown of FAM84B in PDAC cell lines suppressed cell proliferation and induced apoptosis. FAM84B knockdown also suppressed mitochondria! function and glycolysis of PDAC cells. Interestingly, knockdown of FAM84B decreased the nuclear accumulation of beta-catenin, and the expression of c-Myc and lactate dehydrogenase A, but enhanced the expression of Survivin. On the contrary, FAM84B overexpression displayed reversed effects in cell proliferation, apoptosis, mitochondria! function, and glycolysis, which was blocked by the Wnt/beta-catenin pathway inhibitor (XAV939). In addition, PDAC cells with lower expression of FAM84B were more sensitive to gemcitabine-induced cell proliferation inhibition both in vitro and in vivo. In conclusion, FAM84B plays an important role in aerobic glycolysis and tumorigenesis in PDAC and Wnt/beta-catenin may be involved in this process.
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