Oncotarget

Research Papers:

Spermidine/spermine N1-acetyltransferase regulates cell growth and metastasis via AKT/β-catenin signaling pathways in hepatocellular and colorectal carcinoma cells

Cong Wang, Ping Ruan, Ying Zhao, Xiaomin Li, Jun Wang, Xiaoxiao Wu, Tong Liu, Shasha Wang, Jiuzhou Hou, Wei Li, Qian Li, Jinghua Li, Fujun Dai, Dong Fang, Chaojie Wang and Songqiang Xie _

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Oncotarget. 2017; 8:1092-1109. https://doi.org/10.18632/oncotarget.13582

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Abstract

Cong Wang1,*, Ping Ruan1,*, Ying Zhao1, Xiaomin Li1, Jun Wang1, Xiaoxiao Wu1, Tong Liu1, Shasha Wang1, Jiuzhou Hou1, Wei Li1, Qian Li2, Jinghua Li2, Fujun Dai2, Dong Fang1, Chaojie Wang2, Songqiang Xie1

1Institute of Chemical Biology, College of Pharmacy, Henan University, Kaifeng, 475004, China

2The Key Laboratory of Natural Medicine and Immuno-Engineering, Henan University, Kaifeng, 475004, China

*These authors have contributed equally to this work

Correspondence to:

Dong Fang, email: [email protected]

Chaojie Wang, email: [email protected]

Songqiang Xie, email: [email protected]

Keywords: SSAT, polyamine, metastasis, AKT, β-catenin

Received: May 31, 2016    Accepted: November 12, 2016    Published: November 25, 2016

ABSTRACT

Hepatocellular carcinoma (HCC) and colorectal cancer (CRC) are among the most common cancers across the world. Therefore, identifying the potential molecular mechanisms that promote HCC and CRC progression and metastasis are urgently needed. Spermidine/spermine N1-acetyltransferase (SSAT) is a catabolic enzyme that acetylates the high-order polyamines spermine and spermidine, thus decreasing the cellular content of polyamines. Several publications have suggested that depletion of intracellular polyamines inhibited tumor progression and metastasis in various cancer cells. However, whether and how SSAT regulates cell growth, migration and invasion in hepatocellular and colorectal carcinoma cells remains unclear. In this study, depletion of polyamines mediated by SSAT not only attenuated the tumor cell proliferation but also dramatically inhibited cell migration and invasion in hepatocellular and colorectal carcinoma cells. Subsequent investigations revealed introduction of SSAT into HepG2, SMMC7721 hepatocellular carcinoma cells and HCT116 colorectal carcinoma cells significantly suppressed p-AKT, p-GSK3β expression as well as β-catenin nuclear translocation, while inhibition of GSK3β activity or exogenous polyamines could restore SSAT-induced decreases in the protein expression of p-AKT, p-GSK3β and β-catenin. Conversely, knockdown of SSAT in Bel7402 hepatocellular carcinoma cells and HT-29 colorectal carcinoma cells which expressed high levels of SSAT endogenously significantly promoted the expression of p-AKT, p-GSK3β as well as β-catenin nuclear translocation. Taken together, our results indicated depletion of polyamines by SSAT significantly inhibited cell proliferation, migration and invasion through AKT/GSK3β/β-catenin signaling pathway in hepatocellular carcinoma and colorectal cancer cells.


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