2. Academic Validation
  3. Phosphoglucomutase 1 inhibits hepatocellular carcinoma progression by regulating glucose trafficking

Phosphoglucomutase 1 inhibits hepatocellular carcinoma progression by regulating glucose trafficking

  • PLoS Biol. 2018 Oct 18;16(10):e2006483. doi: 10.1371/journal.pbio.2006483.
Guang-Zhi Jin 1,  Yajuan Zhang 2 3,  Wen-Ming Cong 1,  Xueyuan Wu 4,  Xiongjun Wang 2 3,  Siyang Wu 2 3,  Siyao Wang 2 3,  Weiping Zhou 5,  Shengxian Yuan 5,  Hong Gao 2 3,  Guanzhen Yu 6,  Weiwei Yang 2 3
Affiliations

Affiliations

  • 1 Department of Pathology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
  • 2 State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Innovation Center for Cell Signaling Network, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.
  • 3 Shanghai Key Laboratory of Molecular Andrology, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.
  • 4 Department of Radiation Oncology, First Affiliated Hospital of Wenzhou Medical College, Wenzhou, Zhejiang, China.
  • 5 The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
  • 6 Department of Oncology, Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China.
PMID: 30335765 DOI: 10.1371/journal.pbio.2006483
Abstract

Glycogen metabolism commonly altered in Cancer is just beginning to be understood. Phosphoglucomutase 1 (PGM1), the first Enzyme in glycogenesis that catalyzes the reversible conversion between glucose 1-phosphate (G-1-P) and glucose 6-phosphate (G-6-P), participates in both the breakdown and synthesis of glycogen. Here, we show that PGM1 is down-regulated in hepatocellular carcinoma (HCC), which is associated with the malignancy and poor prognosis of HCC. Decreased PGM1 expression obstructed glycogenesis pathway, which leads to the increased flow of glucose into glycolysis, thereby promoting tumor cell proliferation and HCC development. The loss of forkhead box protein J2 (FOXJ2), at least partly due to low genomic copy number in HCC, releases cellular nucleic acid-binding protein (CNBP), a nucleic acid chaperon, to bind to and promote G-quadruplex formation in PGM1 promoter and therefore decreases PGM1 expression. In addition, integrated analyses of PGM1 and FOXJ2 expression provide a better prediction for the malignance and prognosis of HCC. This study establishes a tumor-suppressive role of PGM1 by regulating glucose trafficking and uncovers a novel regulatory mechanism of PGM1 expression.

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