title: Imatinib and bortezomib induce the expression and distribution of anaphase-promoting             complex adaptor protein Cdh1 in blast crisis of chronic myeloid leukemia.
abstract: Anaphase promoting complex cofactor Cdh1 plays a critical role in tumor             suppression and genomic stability in cancer. However, its role in chronic myeloid             leukemia (CML) remains unclear. We treated both wild-type and imatinib-resistant             K562 cells with imatinib or nilotinib and bortezomib, respectively. The siRNAs             of Cdh1 and Skp2 were designed and transiently transfected with HiPerFect transfection             reagent into CML cells. Expression of Cdh1-Skp2-p27 pathway proteins were detected             by Western blotting. Cell cycle, cell apoptosis and cellular morphology were detected             by flow cytometry and Wright staining. Our study revealed that Cdh1 was expressed             at lower levels in imatinib-resistant CML blast crisis (BC) patients than imatinib-sensitive             ones. Moreover, imatinib and bortezomib induced cell cycle quiescence or arrest,             upregulation and nuclear relocation of Cdh1 in CML cells. Furthermore, nilotinib             and bortezomib resulted in upregulation of Cdh1 in imatinib-resistant CML cells.             Conversely, Cdh1 silencing resulted in stabilization of Skp2 and Cdc20, subsequently             promoting G1-S transition and formation of multinucleated cells. Our study shows             that TKIs and bortezomib can regulate the cell cycle and cell apoptosis via regulation             of the expression and redistribution of Cdh1 in CML-BC, which sheds light on the             orchestration of crosstalk between TKIs and bortezomib in imatinib-resistant CML-BC.             Additionally, Cdh1 tends to play an important role in maintenance of genomic stability,             the detailed mechanisms deserve further study.
authors: Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, PR China.
authors: Qiang
authors: Q
authors: Wang
authors: Hong Sheng
authors: HS
authors: Zhou
authors: Kai Kai
authors: KK
authors: Huang
authors: Xue Jie
authors: XJ
authors: Jiang
authors: Fu Qun
authors: FQ
authors: Wu
authors: Rui
authors: R
authors: Cao
authors: Chang Xin
authors: CX
authors: Yin
authors: Li Bin
authors: LB
authors: Liao
authors: Zhong Xin
authors: ZX
authors: Zheng
authors: Han
authors: H
authors: He
authors: Rong
authors: R
authors: Lin
authors: Zheng Shan
authors: ZS
authors: Yi
authors: Dan
authors: D
authors: Xu
authors: Mo
authors: M
authors: Yang
authors: Fan Yi
authors: FY
authors: Meng
mesh_terms: D000328:Adult; D015703:Antigens, CD; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001549:Benzamides; D001752:Blast Crisis; D001897:Boronic Acids / Q000494:pharmacology*; D000069286:Bortezomib; D015820:Cadherins / Q000235:genetics* / Q000378:metabolism; D059447:Cell Cycle Checkpoints; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D019008:Drug Resistance, Neoplasm; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D055785:Gene Knockdown Techniques; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000473:pathology*; D008297:Male; D010879:Piperazines / Q000494:pharmacology* / Q000627:therapeutic use; D011719:Pyrazines / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology* / Q000627:therapeutic use; D034622:RNA Interference; D044786:S-Phase Kinase-Associated Proteins / Q000378:metabolism; D055815:Young Adult
chemical_list: D015703:Antigens, CD; D000970:Antineoplastic Agents; D001549:Benzamides; D001897:Boronic Acids; C513384:CDH1 protein, human; D015820:Cadherins; D010879:Piperazines; D011719:Pyrazines; D011743:Pyrimidines; D044786:S-Phase Kinase-Associated Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D000069286:Bortezomib; D000068877:Imatinib Mesylate