title: Sj7170, a unique dual-function peptide with a specific α-chymotrypsin inhibitory activity and a potent tumor-activating effect from scorpion venom.
abstract: A new peptide precursor, termed Sj7170, was characterized from the venomous gland cDNA library of the scorpion Scorpiops jendeki. Sj7170 was deduced to be a 62-amino acid peptide cross-linked by five disulfide bridges. The recombinant Sj7170 peptide (rSj7170) with chromatographic purity was produced by a prokaryotic expression system. Enzyme inhibition assay in vitro and in vivo showed that rSj7170 specifically inhibited the activity of α-chymotrypsin at micromole concentrations. In addition, Sj7170 not only promoted cell proliferation and colony formation by up-regulating the expression of cyclin D1 in vitro but also enhanced tumor growth in nude mice. Finally, Sj7170 accelerated cellular migration and invasion by increasing the expression of the transcription factor Snail and then inducing the epithelial-mesenchymal transition. Moreover, Sj7170 changed cell morphology and cytoskeleton of U87 cells by the GTPase pathway. Taken together, Sj7170 is a unique dual-function peptide, i.e. a specific α-chymotrypsin inhibitor and a potent tumorigenesis/metastasis activator. Our work not only opens an avenue of developing new modulators of tumorigenesis/metastasis from serine protease inhibitors but also strengthens the functional link between protease inhibitors and tumor activators.
authors.affiliation: State Key Laboratory of Virology, Wuhan University, Wuhan, Hubei 430072, China; College of Life Sciences, Wuhan University, Wuhan, Hubei 430072, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Song
authors.affiliation: College of Life Sciences, Wuhan University, Wuhan, Hubei 430072, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Gong
authors.affiliation: State Key Laboratory of Virology, Wuhan University, Wuhan, Hubei 430072, China; College of Life Sciences, Wuhan University, Wuhan, Hubei 430072, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Yan
authors.affiliation: State Key Laboratory of Virology, Wuhan University, Wuhan, Hubei 430072, China; College of Life Sciences, Wuhan University, Wuhan, Hubei 430072, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Hong
authors.affiliation: State Key Laboratory of Virology, Wuhan University, Wuhan, Hubei 430072, China; College of Life Sciences, Wuhan University, Wuhan, Hubei 430072, China.
authors.forename: Le
authors.initials: L
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Virology, Wuhan University, Wuhan, Hubei 430072, China; College of Life Sciences, Wuhan University, Wuhan, Hubei 430072, China.
authors.forename: Yingliang
authors.initials: Y
authors.lastname: Wu
authors.affiliation: College of Life Sciences, Wuhan University, Wuhan, Hubei 430072, China. Electronic address: whli@whu.edu.cn.
authors.forename: Wenhua
authors.initials: W
authors.lastname: Li
authors.affiliation: State Key Laboratory of Virology, Wuhan University, Wuhan, Hubei 430072, China; College of Life Sciences, Wuhan University, Wuhan, Hubei 430072, China. Electronic address: jpaik@uw.edu.
authors.forename: Wenxin
authors.initials: W
authors.lastname: Li
authors.affiliation: State Key Laboratory of Virology, Wuhan University, Wuhan, Hubei 430072, China; College of Life Sciences, Wuhan University, Wuhan, Hubei 430072, China. Electronic address: zjcao@whu.edu.cn.
authors.forename: Zhijian
authors.initials: Z
authors.lastname: Cao
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002273:Carcinogens / Q000494:pharmacology*; D002918:Chymotrypsin / Q000037:antagonists & inhibitors*; D056741:Cyclin D / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D005822:Genetic Vectors; D008969:Molecular Sequence Data; D011994:Recombinant Proteins / Q000494:pharmacology; D012604:Scorpion Venoms / Q000737:chemistry* / Q000494:pharmacology; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology*
chemical_list: D002273:Carcinogens; D056741:Cyclin D; D018076:DNA, Complementary; D011994:Recombinant Proteins; D012604:Scorpion Venoms; D015842:Serine Proteinase Inhibitors; C000589039:Sj7170 protein, Scorpiops jendeki; D002918:Chymotrypsin; C117608:alpha-chymotrypsin
keywords: Glioblastoma; Metastasis; Peptides; Proliferation; Protease Inhibitor