Hepatocyte growth factor (HGF) upregulates heparanase expression via the PI3K/Akt/NF-κB signaling pathway for gastric cancer metastasis

Cancer Letters
Ning-Bo HaoShi-Ming Yang

Abstract

Heparanase (HPA) is an endoglucuronidase that can promote the shedding of associated cytokines in several types of tumors. However, little is known about what controls the expression of HPA or its role in gastric cancer. In this study, we report for the first time that HGF regulates HPA expression to promote gastric cancer metastasis. In this study, HGF and HPA were found to be significantly expressed in 58 gastric cancer patients. High expression of both HGF and HPA was positively associated with TNM stage, invasion depth and poor prognosis. In MKN74 cells, exogenous HGF significantly increased HPA expression at both the mRNA and protein levels. Further study revealed that HGF first activated PI3K/Akt signaling. NF-κB signaling was activated downstream of PI3K/Akt and promoted HPA expression. However, when c-met, PI3K/Akt or NF-κB signal inhibitors were used, HPA expression was significantly decreased. All of these results indicate that HGF regulates HPA expression by PI3K/Akt and downstream NF-κB signaling. Using bioinformatics and the ChIP assay, p65 was observed to bind to the HPA promoter. Furthermore, HGF significantly induced tumor cell migration, whereas treatment with an NF-κB inhibitor decreased migration. Moreover, w...Continue Reading

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Citations

Jul 28, 2016·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Zhi-Yuan FanMin Yan
Dec 29, 2017·Journal of Experimental & Clinical Cancer Research : CR·Yanxia HuangJinshui Zhu
Feb 27, 2016·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Ye ZhangHonglu Wu
Jul 9, 2020·Journal of Leukocyte Biology·Shanshan LiYuhong Bian
Mar 30, 2017·Toxins·Olga Sokolova, Michael Naumann
Jun 6, 2017·Laboratory Investigation; a Journal of Technical Methods and Pathology·Xin Liu, Kent-Man Chu
Dec 2, 2020·Journal of Translational Medicine·Krishnath M Jayatilleke, Mark D Hulett
Feb 20, 2021·The FEBS Journal·Nikos K KaramanosMaurizio Onisto
Jul 6, 2021·Frontiers in Immunology·Li TangShiming Yang
Aug 4, 2021·Neoplasia : an International Journal for Oncology Research·Jingjing LiuIsrael Vlodavsky

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