Genetic and molecular analyses reveal G6PC as a key element connecting glucose metabolism and cell cycle control in ovarian cancer.
We aimed to evaluate the role of glucose-6-phosphatase, catalytic subunit (G6PC) in ovarian cancer and to exploit its therapeutic potential. With reproduction of The Cancer Genome Atlas (TCGA) database, we studied expressions of genes in the glucose metabolism pathways in silico. The cBioPortal For Cancer Genomics was used to study the clinical, pathological and molecular profiles of G6PC. In vitro studies were performed to validate the function of G6PC and the effect of genetic and pharmaceutical G6PC inhibition. In 158 ovarian cancer (OvCa) patients with complete RNA-seq data, G6PC expression was increased in 27 patients (17 %). Both overall survival (OS) and disease-free period were significantly shorter in cases with increased G6PC level. Significantly decreased total and phosphorylated CDKN1B level was noted in OvCa with increased G6PC expression. Silenced G6PC in OvCa cells induced decreased cell proliferation, viability, invasiveness and anchorage-independent cell growth. G6PC silencing also induced enhanced cell cycle control proteins and restoration of CDKN1B level. Pharmaceutical inhibition of G6PC with specific compound showed similar effects to genetic silencing. G6PC played dual roles both in glucose metabolism and cell cycle control in OvCa, which potentiated it a promising therapeutic target.
Department of Gynaecology, Obstetrics and Gynaecology Hospital, Fudan University, Shanghai, 200011, People's Republic of China.
Ting
T
Guo
Department of Stem Cell and and Regenerative Biology, Harvard University, 7 Divinity Avenue, Cambridge, MA, 02138, USA.
Tao
T
Chen
Department of Gynaecology, Obstetrics and Gynaecology Hospital, Fudan University, Shanghai, 200011, People's Republic of China.
Chao
C
Gu
Department of Gynaecology, Obstetrics and Gynaecology Hospital, Fudan University, Shanghai, 200011, People's Republic of China.
Bin
B
Li
Department of Gynaecology, Obstetrics and Gynaecology Hospital, Fudan University, Shanghai, 200011, People's Republic of China. drxucongjian@163.com.
Congjian
C
Xu
D020134:Catalytic Domain / Q000235:genetics; D059447:Cell Cycle Checkpoints / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D020868:Gene Silencing / Q000502:physiology; D005947:Glucose / Q000378:metabolism*; D005952:Glucose-6-Phosphatase / Q000235:genetics*; D006801:Humans; D010051:Ovarian Neoplasms / Q000235:genetics*; D010766:Phosphorylation / Q000235:genetics
C436291:CDKN1B protein, human; D018797:Cell Cycle Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D005952:Glucose-6-Phosphatase; D005947:Glucose
CDKN1B; Cell cycle; G6PC; Glucose metabolism; Ovarian cancer