title: SUMOylation of insulin-like growth factor 1 receptor, promotes proliferation in acute myeloid leukemia.
abstract: Current valid treatments for acute myeloid leukemia (AML) include chemotherapy and hematopoietic stem cell transplantation, which are defective and limited respectively. The insulin-like growth factor 1 receptor (IGF-1R) is up-regulated in many solid tumors; therefore, it may be a target for tumor therapy. Interestingly, IGF-1R is modified by SUMOylation, a type of reversible post-translational modification. In this study, we found that IGF-1R was increased in both cell lines and clinical samples of AML and was modified by SUMO-1. Furthermore, IGF-1, ligand of IGF-1R, induced the up-regulation of IGF-1R and increased the proliferation of leukemia cell line. After mutation of Lys(1025) and Lys(1100) in IGF-1R, the evolutionarily conserved lysine residues were identified as the SUMOylation sites of IGF-1R, because the SUMOylation of IGF-1R in these mutants was significantly inhibited. Furthermore, the cell proliferation mediated by IGF-1 was also reduced. After inhibition of UBC9, the activating enzyme of SUMOylation, co-expression of IGF-1R and SUMO-1 was down-regulated, and cell proliferation was also inhibited. However, cell apoptosis was not significantly affected. These results suggest that IGF-1R and its SUMOylation may be a new therapeutic target for strategy of AML.
authors.affiliation: Department of Hematology, Xiang-Ya Hospital, Central South University, 87 Xiang-Ya Road, Changsha 410008, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Hematology, Zhong-Shan Hospital, Xiamen University, Xiamen, China.
authors.forename: Fang-Fang
authors.initials: FF
authors.lastname: Huang
authors.affiliation: Department of Hematology, Xiang-Ya Hospital, Central South University, 87 Xiang-Ya Road, Changsha 410008, China.
authors.forename: Deng-Shu
authors.initials: DS
authors.lastname: Wu
authors.affiliation: Department of Hematology, Xiang-Ya Hospital, Central South University, 87 Xiang-Ya Road, Changsha 410008, China.
authors.forename: Wen-Jin
authors.initials: WJ
authors.lastname: Li
authors.affiliation: Department of Hematology, Xiang-Ya Hospital, Central South University, 87 Xiang-Ya Road, Changsha 410008, China.
authors.forename: Hui-En
authors.initials: HE
authors.lastname: Zhan
authors.affiliation: Department of Hematology, Xiang-Ya Hospital, Central South University, 87 Xiang-Ya Road, Changsha 410008, China.
authors.forename: Min-Yuan
authors.initials: MY
authors.lastname: Peng
authors.affiliation: Department of Hematology, Xiang-Ya Hospital, Central South University, 87 Xiang-Ya Road, Changsha 410008, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Fang
authors.affiliation: Department of Hematology, Xiang-Ya Hospital, Central South University, 87 Xiang-Ya Road, Changsha 410008, China.
authors.forename: Peng-Fei
authors.initials: PF
authors.lastname: Cao
authors.affiliation: Department of Hematology, Xiang-Ya Hospital, Central South University, 87 Xiang-Ya Road, Changsha 410008, China.
authors.forename: Meng-Meng
authors.initials: MM
authors.lastname: Zhang
authors.affiliation: Department of Hematology, Xiang-Ya Hospital, Central South University, 87 Xiang-Ya Road, Changsha 410008, China. Electronic address: androps2011@hotmail.com.
authors.forename: Hui
authors.initials: H
authors.lastname: Zeng
authors.affiliation: Department of Hematology, Xiang-Ya Hospital, Central South University, 87 Xiang-Ya Road, Changsha 410008, China. Electronic address: xychenfp@hotmail.com.
authors.forename: Fang-Ping
authors.initials: FP
authors.lastname: Chen
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000502:physiology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D017526:Receptor, IGF Type 1 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D058207:Sumoylation; D055815:Young Adult
chemical_list: D017526:Receptor, IGF Type 1
keywords: Acute myeloid leukemia; Insulin-like growth factor receptor; SUMOylation; Targeted therapy