title: Quantitative Proteomic Profiling of Tachyplesin I Targets in U251 Gliomaspheres.
abstract: Tachyplesin I is a cationic peptide isolated from hemocytes of the horseshoe crab and its anti-tumor activity has been demonstrated in several tumor cells. However, there is limited information providing the global effects and mechanisms of tachyplesin I on glioblastoma multiforme (GBM). Here, by using two complementary proteomic strategies (2D-DIGE and dimethyl isotope labeling-based shotgun proteomics), we explored the effect of tachyplesin I on the proteome of gliomaspheres, a three-dimensional growth model formed by a GBM cell line U251. In total, the expression levels of 192 proteins were found to be significantly altered by tachyplesin I treatment. Gene ontology (GO) analysis revealed that many of them were cytoskeleton proteins and lysosomal acid hydrolases, and the mostly altered biological process was related to cellular metabolism, especially glycolysis. Moreover, we built protein-protein interaction network of these proteins and suggested the important role of DNA topoisomerase 2-alpha (TOP2A) in the signal-transduction cascade of tachyplesin I. In conclusion, we propose that tachyplesin I might down-regulate cathepsins in lysosomes and up-regulate TOP2A to inhibit migration and promote apoptosis in glioma, thus contribute to its anti-tumor function. Our results suggest tachyplesin I is a potential candidate for treatment of glioma.
authors.affiliation: School of Applied Chemistry and Biotechnology, Shenzhen Polytechnic, No. 2190 Liuxian Road, Nanshan District, Shenzhen 518055, Guangdong, China. smilelixuan@163.com.
authors.forename: Xuan
authors.initials: X
authors.lastname: Li
authors.affiliation: School of Applied Chemistry and Biotechnology, Shenzhen Polytechnic, No. 2190 Liuxian Road, Nanshan District, Shenzhen 518055, Guangdong, China. jgdai@szpt.edu.cn.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Dai
authors.affiliation: School of Applied Chemistry and Biotechnology, Shenzhen Polytechnic, No. 2190 Liuxian Road, Nanshan District, Shenzhen 518055, Guangdong, China. tangyongjun@szpt.edu.cn.
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Tang
authors.affiliation: School of Applied Chemistry and Biotechnology, Shenzhen Polytechnic, No. 2190 Liuxian Road, Nanshan District, Shenzhen 518055, Guangdong, China. lilulu011071@hotmail.com.
authors.forename: Lulu
authors.initials: L
authors.lastname: Li
authors.affiliation: School of Applied Chemistry and Biotechnology, Shenzhen Polytechnic, No. 2190 Liuxian Road, Nanshan District, Shenzhen 518055, Guangdong, China. jingang@szpt.edu.cn.
authors.forename: Gang
authors.initials: G
authors.lastname: Jin
mesh_terms: D000951:Antigens, Neoplasm / Q000378:metabolism; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002403:Cathepsins / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D004250:DNA Topoisomerases, Type II / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D005909:Glioblastoma / Q000188:drug therapy / Q000378:metabolism; D005910:Glioma / Q000188:drug therapy* / Q000378:metabolism*; D006019:Glycolysis / Q000187:drug effects; D006801:Humans; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism; D010456:Peptides, Cyclic / Q000494:pharmacology*; D000075223:Poly-ADP-Ribose Binding Proteins; D020543:Proteome / Q000378:metabolism*; D040901:Proteomics / Q000379:methods; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000951:Antigens, Neoplasm; D023181:Antimicrobial Cationic Peptides; D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D010456:Peptides, Cyclic; D000075223:Poly-ADP-Ribose Binding Proteins; D020543:Proteome; C057636:tachyplesin peptide, Tachypleus tridentatus; D002403:Cathepsins; D004250:DNA Topoisomerases, Type II; C000618811:TOP2A protein, human
keywords: cancer stem cell; glioblastoma multiforme; parallel reaction monitoring; stable isotope dimethyl labeling; tachyplesin I