PMID- 33571515 OWN - NLM STAT- MEDLINE DCOM- 20211215 LR - 20221207 IS - 1879-0631 (Electronic) IS - 0024-3205 (Linking) VI - 287 DP - 2021 Dec 15 TI - Fam83D promotes tumorigenesis and gemcitabine resistance of pancreatic adenocarcinoma through the Wnt/beta-catenin pathway. PG - 119205 LID - S0024-3205(21)00190-9 [pii] LID - 10.1016/j.lfs.2021.119205 [doi] AB - 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 beta-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/beta-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/beta-catenin signaling. CI - Copyright (c) 2021. Published by Elsevier Inc. FAU - Hua, Yong-Qiang AU - Hua YQ AD - 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. FAU - Zhang, Ke AU - Zhang K AD - 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. FAU - Sheng, Jie AU - Sheng J AD - 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. FAU - Ning, Zhou-Yu AU - Ning ZY AD - 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. FAU - Li, Ye AU - Li Y AD - 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. FAU - Shi, Wei-Dong AU - Shi WD AD - Minimally Invasive Treatment Center, Fudan University Shanghai Cancer Center, 270 Dong An Road, Shanghai 200032, PR China. FAU - Liu, Lu-Ming AU - Liu LM AD - 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. LA - eng PT - Journal Article DEP - 20210208 PL - Netherlands TA - Life Sci JT - Life sciences JID - 0375521 RN - 0 (Cell Cycle Proteins) RN - 0 (FAM83D protein, human) RN - 0 (Microtubule-Associated Proteins) RN - 0W860991D6 (Deoxycytidine) RN - 0 (Gemcitabine) SB - IM MH - Adenocarcinoma/drug therapy/*metabolism MH - Aged MH - Animals MH - Carcinogenesis/drug effects/*metabolism MH - Cell Cycle Proteins/*biosynthesis MH - Deoxycytidine/*analogs & derivatives/pharmacology/therapeutic use MH - Drug Resistance, Neoplasm/drug effects/physiology MH - Female MH - Humans MH - Male MH - Mice MH - Mice, Nude MH - Microtubule-Associated Proteins/*biosynthesis MH - Middle Aged MH - Pancreatic Neoplasms/drug therapy/*metabolism MH - Wnt Signaling Pathway/drug effects/*physiology MH - Xenograft Model Antitumor Assays/methods MH - Gemcitabine OTO - NOTNLM OT - Chemoresistance OT - Fam83D OT - Glycolysis OT - Pancreatic adenocarcinoma OT - beta-Catenin EDAT- 2021/02/12 06:00 MHDA- 2021/12/16 06:00 CRDT- 2021/02/11 20:10 PHST- 2020/12/10 00:00 [received] PHST- 2021/01/29 00:00 [revised] PHST- 2021/02/05 00:00 [accepted] PHST- 2021/02/12 06:00 [pubmed] PHST- 2021/12/16 06:00 [medline] PHST- 2021/02/11 20:10 [entrez] AID - S0024-3205(21)00190-9 [pii] AID - 10.1016/j.lfs.2021.119205 [doi] PST - ppublish SO - Life Sci. 2021 Dec 15;287:119205. doi: 10.1016/j.lfs.2021.119205. Epub 2021 Feb 8.