Oncotarget

Research Papers:

PIM1 regulates glycolysis and promotes tumor progression in hepatocellular carcinoma

Carmen Oi-ning Leung, Carmen Chak-lui Wong, Dorothy Ngo-yin Fan, Alan Ka-lun Kai, Edmund Kwok-kwan Tung, Iris Ming-jing Xu, Irene Oi-lin Ng and Regina Cheuk-lam Lo _

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Oncotarget. 2015; 6:10880-10892. https://doi.org/10.18632/oncotarget.3534

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Abstract

Carmen Oi-ning Leung1, Carmen Chak-lui Wong1,2, Dorothy Ngo-yin Fan1, Alan Ka-lun Kai1, Edmund Kwok-kwan Tung1, Iris Ming-jing Xu1, Irene Oi-lin Ng1,2 and Regina Cheuk-lam Lo1,2

1 Department of Pathology, The University of Hong Kong, Hong Kong, China

2 State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong, China

Correspondence to:

Regina Cheuk-lam Lo, email:

Irene Oi-lin Ng, email:

Keywords: PIM1, HCC, metastasis

Received: October 30, 2014 Accepted: February 18, 2015 Published: March 12, 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.


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