Fam83D promotes tumorigenesis and gemcitabine resistance of pancreatic adenocarcinoma through the Wnt/β-catenin pathway.

Autor: Hua YQ; Minimally Invasive Treatment Center, Fudan University Shanghai Cancer Center, 270 Dong An Road, Shanghai 200032, PR China; Department of Oncology, Shanghai Medical College, Fudan University, 270 Dong An Road, Shanghai 200032, PR China., Zhang K; Minimally Invasive Treatment Center, Fudan University Shanghai Cancer Center, 270 Dong An Road, Shanghai 200032, PR China; Department of Oncology, Shanghai Medical College, Fudan University, 270 Dong An Road, Shanghai 200032, PR China., Sheng J; Minimally Invasive Treatment Center, Fudan University Shanghai Cancer Center, 270 Dong An Road, Shanghai 200032, PR China; Department of Oncology, Shanghai Medical College, Fudan University, 270 Dong An Road, Shanghai 200032, PR China., Ning ZY; Minimally Invasive Treatment Center, Fudan University Shanghai Cancer Center, 270 Dong An Road, Shanghai 200032, PR China; Department of Oncology, Shanghai Medical College, Fudan University, 270 Dong An Road, Shanghai 200032, PR China., Li Y; Minimally Invasive Treatment Center, Fudan University Shanghai Cancer Center, 270 Dong An Road, Shanghai 200032, PR China; Department of Oncology, Shanghai Medical College, Fudan University, 270 Dong An Road, Shanghai 200032, PR China., Shi WD; Minimally Invasive Treatment Center, Fudan University Shanghai Cancer Center, 270 Dong An Road, Shanghai 200032, PR China., Liu LM; Minimally Invasive Treatment Center, Fudan University Shanghai Cancer Center, 270 Dong An Road, Shanghai 200032, PR China; Department of Oncology, Shanghai Medical College, Fudan University, 270 Dong An Road, Shanghai 200032, PR China. Electronic address: liuluming2018@163.com.
Jazyk: angličtina
Zdroj: Life sciences [Life Sci] 2021 Dec 15; Vol. 287, pp. 119205. Date of Electronic Publication: 2021 Feb 08.
DOI: 10.1016/j.lfs.2021.119205
Abstrakt: Background: Elevated expression of family with sequence similarity 83 member D (Fam83D) has been found in various cancers; however, its role in pancreatic adenocarcinoma (PDAC) remains unclear. The current study was designed to elucidate the roles of Fam83D in pancreatic cancer.
Method: The level of Fam83D was detected in PDAC tissues and adjacent no-tumorous tissues. Effects of Fam83D on proliferation, glycolysis and gemcitabine (GEM) sensitivity of pancreatic cancer cells were examined.
Results: Fam83D was overexpressed in PDAC and associated with clinical stage, metastatic status and survival rates of PDAC patients. Function study showed that Fam83D knockdown (KD) caused inhibited proliferation, suppressed mitochondrial respiration capacity, reduced aerobic glycolysis, and down-regulation of nuclear β-catenin, proto-oncogene C-Myc, and lactate dehydrogenase A (LDHA). Fam83D KD enhanced the sensitivity of PDAC cells to GEM in vitro and in vivo. On the contrary, Fam83D overexpression displayed reverse effects on PDAC cells. Moreover, the Wnt/β-catenin inhibitor abolished the effects of Fam83D overexpression in PDAC cells.
Conclusions: the current data suggest that enhanced Fam83D expression contributes to PDAC progression and the development of chemoresistance through the Wnt/β-catenin signaling.
(Copyright © 2021. Published by Elsevier Inc.)
Databáze: MEDLINE
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