title: A new facet of NDRG1 in pancreatic ductal adenocarcinoma: Suppression of glycolytic metabolism.
abstract: N-myc downstream-regulated gene 1 (NDRG1) is known as tumor/metastasis suppressor in a variety of cancers including pancreas, being involved in angiogenesis, cancer growth and metastasis. However, the precise molecular mechanism how NDRG1 exerts its inhibitory function in pancreatic cancer remains unclear. In this investigation, we demonstrated that K-Ras plays a vital role in modulating NDRG1 protein level in PDAC cancer cells in vitro, which is mediated through ERK signaling. Noteworthy, K-Ras downstream Akt/mTOR signaling is inhibited upon NDRG1 overexpression, resulting in decease of HIF1α level. Moreover, NDRG1 has a unique role in modulating cancer metabolism of pancreatic ductal adenocarcinoma (PDAC). The mechanism accounting for NDRG1 in modulating aerobic glycolysis, at least partly, relied on its regulation of glycolysis genes including GLUT1, HK2, LDHA and PDK1. Additionally, NDRG1 is shown to suppress the activity of HIF1α, which is responsible for regulation of glycolysis enzymes. The current study is the first to elucidate a unique facet of the potent tumor/metastasis suppressor NDRG1 in the regulation of PDAC glycolysis, leading to important insights into the mechanism by which NDRG1 exert inhibitory function in PDAC.
authors.affiliation: Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, P.R. China.
authors.forename: Wensheng
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, P.R. China.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, P.R. China.
authors.forename: Qiangsheng
authors.initials: Q
authors.lastname: Hu
authors.affiliation: Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, P.R. China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Qin
authors.affiliation: Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, P.R. China.
authors.forename: Wenyan
authors.initials: W
authors.lastname: Xu
authors.affiliation: Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, P.R. China.
authors.forename: Si
authors.initials: S
authors.lastname: Shi
authors.affiliation: Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, P.R. China.
authors.forename: Chen
authors.initials: C
authors.lastname: Liang
authors.affiliation: Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, P.R. China.
authors.forename: Qingcai
authors.initials: Q
authors.lastname: Meng
authors.affiliation: Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, P.R. China.
authors.forename: Jinfeng
authors.initials: J
authors.lastname: Xiang
authors.affiliation: Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, P.R. China.
authors.forename: Dingkong
authors.initials: D
authors.lastname: Liang
authors.affiliation: Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, P.R. China.
authors.forename: Shunrong
authors.initials: S
authors.lastname: Ji
authors.affiliation: Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, P.R. China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Liu
authors.affiliation: Pancreatic Cancer Institute, Fudan University, Shanghai, P.R. China.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Hu
authors.affiliation: Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, P.R. China.
authors.forename: Liang
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, P.R. China.
authors.forename: Chen
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, P.R. China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Long
authors.affiliation: Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, P.R. China.
authors.forename: Quanxing
authors.initials: Q
authors.lastname: Ni
authors.affiliation: Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, P.R. China.
authors.forename: Xianjun
authors.initials: X
authors.lastname: Yu
authors.affiliation: Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, P.R. China.
authors.forename: Jin
authors.initials: J
authors.lastname: Xu
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics* / Q000473:pathology; D018797:Cell Cycle Proteins / Q000096:biosynthesis / Q000235:genetics*; D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006019:Glycolysis / Q000235:genetics*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins / Q000096:biosynthesis / Q000235:genetics*; D020935:MAP Kinase Signaling System / Q000235:genetics; D008297:Male; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000235:genetics; D000099259:N-myc Downstream-Regulated Gene 1 Protein
chemical_list: D018797:Cell Cycle Proteins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D047908:Intracellular Signaling Peptides and Proteins; D009363:Neoplasm Proteins; D000099259:N-myc Downstream-Regulated Gene 1 Protein; C497442:HIF1A protein, human