The pentapeptide Gly-Thr-Gly-Lys-Thr confers sensitivity to anti-cancer drugs by inhibition of CAGE binding to GSK3β and decreasing the expression of cyclinD1

被引：14

作者：

Kim, Youngmi ^{[1
]}

Kim, Hyuna ^{[1
]}

Park, Deokbum ^{[1
]}

Lee, Hansoo ^{[2
]}

Lee, Yun Sil ^{[3
]}

Choe, Jongseon ^{[4
]}

Kim, Young Myeong ^{[4
]}

Jeon, Doyong ^{[5
]}

Jeoung, Dooil ^{[1
]}

机构：

[1] Kangwon Natl Univ, Coll Nat Sci, Dept Biochem, Chunchon 24341, South Korea

[2] Kangwon Natl Univ, Coll Nat Sci, Dept Biol Sci, Chunchon 24341, South Korea

[3] Ewha Womans Univ, Coll Pharm, Seoul 03760, South Korea

[4] Kangwon Natl Univ, Grad Sch Med, Chunchon 24341, South Korea

[5] L Base Co, Seoul 01062, South Korea

来源：

ONCOTARGET | 2017年 / 8卷 / 08期

基金：

新加坡国家研究基金会;

关键词：

anti-cancer drug-resistance; CAGE; cyclinD1; GSK3; beta; peptides; CANCER/TESTIS ANTIGEN CAGE; TUMOR-CELL GROWTH; FEEDBACK LOOP; BETA-CATENIN; GENE CAGE; IN-VIVO; PEPTIDE; CANCER; D1; PHOSPHORYLATION;

D O I：

10.18632/oncotarget.14621

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

We previously reported the role of cancer/testis antigen CAGE in the response to anti-cancer drugs. CAGE increased the expression of cyclinD1, and pGSK3 beta(Ser9), an inactive GSK3 beta, while decreasing the expression of phospho-cyclinD1Thr(286). CAGE showed binding to GSK3 beta and the domain of CAGE (amino acids 231-300) necessary for binding to GSK3 beta and for the expression regulation of cyclinD1 was determined. (269)GTGKT(273) peptide, corresponding to the DEAD box helicase domain of CAGE, decreased the expression of cyclinD1 and pGSK3 beta(Ser9) while increasing the expression of phosphocyclinD1(Thr286). GTGKT peptide showed the binding to CAGE and prevented CAGE from binding to GSK3 beta. GTGKT peptide changed the localization of CAGE and inhibited the binding of CAGE to the promoter sequences of cyclin D1. GTGKT peptide enhanced the apoptotic effects of anti-cancer drugs and decreased the migration, invasion, angiogenic, tumorigenic and metastatic potential of anti-cancer drug-resistant cancer cells. We found that Lys(272) of GTGKT peptide was necessary for conferring anti-cancer activity. Peptides corresponding to the DEAD box helicase domain of CAGE, such as AQTGTGKT, QTGTGKT and TGTGKT, also showed anti-cancer activity by preventing CAGE from binding to GSK3 beta. GTGKT peptide showed ex vivo tumor homing potential. Thus, peptides corresponding to the DEAD box helicase domain of CAGE can be developed as anti-cancer drugs in cancer patients expressing CAGE.

引用

页码：13632 / 13651

页数：20