title: Spermidine/spermine N1-acetyltransferase regulates cell growth and metastasis via AKT/β-catenin signaling pathways in hepatocellular and colorectal carcinoma cells.
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.
authors.affiliation: Institute of Chemical Biology, College of Pharmacy, Henan University, Kaifeng, 475004, China.
authors.forename: Cong
authors.initials: C
authors.lastname: Wang
authors.affiliation: Institute of Chemical Biology, College of Pharmacy, Henan University, Kaifeng, 475004, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Ruan
authors.affiliation: Institute of Chemical Biology, College of Pharmacy, Henan University, Kaifeng, 475004, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Institute of Chemical Biology, College of Pharmacy, Henan University, Kaifeng, 475004, China.
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Li
authors.affiliation: Institute of Chemical Biology, College of Pharmacy, Henan University, Kaifeng, 475004, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: Institute of Chemical Biology, College of Pharmacy, Henan University, Kaifeng, 475004, China.
authors.forename: Xiaoxiao
authors.initials: X
authors.lastname: Wu
authors.affiliation: Institute of Chemical Biology, College of Pharmacy, Henan University, Kaifeng, 475004, China.
authors.forename: Tong
authors.initials: T
authors.lastname: Liu
authors.affiliation: Institute of Chemical Biology, College of Pharmacy, Henan University, Kaifeng, 475004, China.
authors.forename: Shasha
authors.initials: S
authors.lastname: Wang
authors.affiliation: Institute of Chemical Biology, College of Pharmacy, Henan University, Kaifeng, 475004, China.
authors.forename: Jiuzhou
authors.initials: J
authors.lastname: Hou
authors.affiliation: Institute of Chemical Biology, College of Pharmacy, Henan University, Kaifeng, 475004, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: The Key Laboratory of Natural Medicine and Immuno-Engineering, Henan University, Kaifeng, 475004, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Li
authors.affiliation: The Key Laboratory of Natural Medicine and Immuno-Engineering, Henan University, Kaifeng, 475004, China.
authors.forename: Jinghua
authors.initials: J
authors.lastname: Li
authors.affiliation: The Key Laboratory of Natural Medicine and Immuno-Engineering, Henan University, Kaifeng, 475004, China.
authors.forename: Fujun
authors.initials: F
authors.lastname: Dai
authors.affiliation: Institute of Chemical Biology, College of Pharmacy, Henan University, Kaifeng, 475004, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Fang
authors.affiliation: The Key Laboratory of Natural Medicine and Immuno-Engineering, Henan University, Kaifeng, 475004, China.
authors.forename: Chaojie
authors.initials: C
authors.lastname: Wang
authors.affiliation: Institute of Chemical Biology, College of Pharmacy, Henan University, Kaifeng, 475004, China.
authors.forename: Songqiang
authors.initials: S
authors.lastname: Xie
mesh_terms: D000123:Acetyltransferases / Q000235:genetics / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism; D011073:Polyamines / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction; D014410:Tumor Stem Cell Assay; D051176:beta Catenin / Q000378:metabolism*; D000099228:Diamine N-Acetyltransferase
chemical_list: D000123:Acetyltransferases; D011073:Polyamines; D051057:Proto-Oncogene Proteins c-akt; D051176:beta Catenin; D000099228:Diamine N-Acetyltransferase
keywords: AKT; SSAT; metastasis; polyamine; β-catenin