Back to Search
Start Over
PIM1 regulates glycolysis and promotes tumor progression in hepatocellular carcinoma.
- Source :
-
Oncotarget [Oncotarget] 2015 May 10; Vol. 6 (13), pp. 10880-92. - Publication Year :
- 2015
-
Abstract
- Hepatocellular carcinoma (HCC) is characteristically one of the most rapidly proliferating tumors which outgrows functional blood supply and results in regional oxygen deprivation. Overexpression of PIM1, a serine/threonine kinase, has been identified recently in human cancers. Knowledge on PIM1 in HCC is however, scarce. By immunohistochemical analysis on 56 human primary HCC samples, we observed overexpression of PIM1 in 39% of the cases. In two independent cohorts of paired primary and extra-hepatic metastatic HCC tissues, PIM1 expression was higher (p=0.002) in the extra-hepatic metastatic HCC tissues as compared with the corresponding primary HCCs. PIM1 was markedly up-regulated in multiple HCC cell lines in hypoxic condition (1% O2) versus normoxia (20% O2). Silencing of PIM1 suppressed HCC cell invasion in vitro as compared to non-target control, and decreased HCC cell proliferation in vitro and tumor growth and metastatic potential in vivo. Knockdown of PIM1 significantly reduced glucose uptake by HCC cells and was associated with decreased levels of p-AKT and key molecules in the glycolytic pathway. Taken together, PIM1 is up-regulated by hypoxia in HCC and promotes tumor growth and metastasis through facilitating cancer cell glycolysis. Targeting PIM1 may have potential role in the management of HCC.
- Subjects :
- Active Transport, Cell Nucleus
Aged
Aged, 80 and over
Animals
Carcinoma, Hepatocellular genetics
Carcinoma, Hepatocellular secondary
Cell Hypoxia
Cell Line, Tumor
Cell Movement
Cell Proliferation
Disease Progression
Female
Gene Expression Regulation, Neoplastic
Gene Knockdown Techniques
Humans
Hypoxia-Inducible Factor 1, alpha Subunit metabolism
Liver Neoplasms genetics
Liver Neoplasms pathology
Male
Mice, Nude
Middle Aged
Neoplasm Invasiveness
Phosphorylation
Proteasome Endopeptidase Complex metabolism
Proteolysis
Proto-Oncogene Proteins c-akt metabolism
Proto-Oncogene Proteins c-pim-1 genetics
RNA Interference
Signal Transduction
Time Factors
Transfection
Tumor Burden
Up-Regulation
Carcinoma, Hepatocellular enzymology
Glycolysis
Liver Neoplasms enzymology
Proto-Oncogene Proteins c-pim-1 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1949-2553
- Volume :
- 6
- Issue :
- 13
- Database :
- MEDLINE
- Journal :
- Oncotarget
- Publication Type :
- Academic Journal
- Accession number :
- 25834102
- Full Text :
- https://doi.org/10.18632/oncotarget.3534