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