Abstract
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 mitochondrial function and glycolysis of PDAC cells. Interestingly, knockdown of FAM84B decreased the nuclear accumulation of β-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, mitochondrial function, and glycolysis, which was blocked by the Wnt/β-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/β-catenin may be involved in this process.
Highlights
Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal human malignancy with an extremely poor fiveyear survival rate [1]
By analyzing The Cancer Genome Atlas cohort, we found that FAM84B amplification was observed in 11% of 141 pancreatic ductal adenocarcinoma (PDAC) patients, and FAM84B amplification was correlated with higher mRNA expression of FAM84B
Data from The Cancer Genome Atlas (TCGA, https://tcga-data.nci.nih.gov/tcga) on pancreatic ductal adenocarcinoma (PDAC) indicated FAM84B amplification in 11% of 141 PDAC patients, while no amplification was observed for FAM84A (Figure 1A)
Summary
Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal human malignancy with an extremely poor fiveyear survival rate [1]. The risk factors of PDAC include smoking, diabetes, obesity, and pancreatitis [2]. The prognosis of PDAC remains poor because minimal progress has been made in early diagnosis, prevention, and treatment of patients with PDAC [9,10,11]. More than 80% of PDAC patients have advanced disease when first diagnosed [1]. Gemcitabine remains the standard agent for the treatment of advanced PDAC, but acquired resistance within weeks of chemotherapy initiation limits the treatment potency and leads to the poor prognosis [12]. Research on the molecular basis of gemcitabine www.aging-us.com resistance may help increase the efficacy of chemotherapy and improve the clinical outcomes
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