title: Imp2 regulates GBM progression by activating IGF2/PI3K/Akt pathway.
abstract: Glioblastomas multiforme (GBM) are the most frequently occurring malignant brain cancers. Treatment for GBM consists of surgical resection and subsequent adjuvant radiation therapy and chemotherapy. Despite this, GBM patient survival is limited to 12-15 months, and researchers are continually trying to develop improved therapy options. Insulin-like growth factor 2 mRNA-binding protein 2 (Imp2) is known to be upregulated in many cancers and is known to regulate the signaling activity of insulin-like growth factor 2 (IGF2). However, relatively little is known about its role in malignant development of GBM. In this study, we first found Imp2 is upregulated in GBM tissues by using clinical samples and public database search. Studies with loss and gain of Imp2 expression in in vitro GBM cell culture system demonstrated the role of Imp2 in promoting GBM cell proliferation, migration, invasion and epithelial-to-mesenchymal transition (EMT). Additionally, our results show that Imp2 regulates the activity of IGF2, which further activates PI3K/Akt signaling, thereby to promote GBM malignancy. Inhibition of Imp2 was also found to sensitize GBM to temozolomide treatment. These observations add to the current knowledge of GBM biology, and may prove useful in development of more effective GBM therapy.
authors.affiliation: a Department of Neurosurgery; The First Hospital of Jilin University ; Changchun , Jilin , China.
authors.forename: Qingchun
authors.initials: Q
authors.lastname: Mu
authors.forename: Lijun
authors.initials: L
authors.lastname: Wang
authors.forename: Fengbo
authors.initials: F
authors.lastname: Yu
authors.forename: Haijun
authors.initials: H
authors.lastname: Gao
authors.forename: Ting
authors.initials: T
authors.lastname: Lei
authors.forename: Peiwen
authors.initials: P
authors.lastname: Li
authors.forename: Pengfei
authors.initials: P
authors.lastname: Liu
authors.forename: Xu
authors.initials: X
authors.lastname: Zheng
authors.forename: Xitong
authors.initials: X
authors.lastname: Hu
authors.forename: Yong
authors.initials: Y
authors.lastname: Chen
authors.forename: Zhenfeng
authors.initials: Z
authors.lastname: Jiang
authors.forename: Arash J
authors.initials: AJ
authors.lastname: Sayari
authors.forename: Jia
authors.initials: J
authors.lastname: Shen
authors.forename: Haiyan
authors.initials: H
authors.lastname: Huang
mesh_terms: D001932:Brain Neoplasms / Q000188:drug therapy / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D003606:Dacarbazine / Q000031:analogs & derivatives / Q000494:pharmacology; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy / Q000235:genetics*; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics*; D016601:RNA-Binding Proteins / Q000235:genetics*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D000077204:Temozolomide; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
chemical_list: C035170:IGF2 protein, human; C498779:IGF2BP2 protein, human; D016601:RNA-Binding Proteins; D007335:Insulin-Like Growth Factor II; D003606:Dacarbazine; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D000077204:Temozolomide
keywords: Akt; E-cadherin; EMT; EMT, epithelial-mesenchymal transition; GBM; GBM, glioblastomas multiforme; GBM-P, semi-established GBM primary cells; GBM-RE, semi-established recurrent TMZ-resistant GBM primary cells; IGF2; IGF2, insulin-like growth factor 2; Imp2; Imp2, insulin-like growth factor 2 mRNA-binding protein 2; KD, knockdown; N-cadherin; OE, overexpressing; PI3K; PI3K, phosphatidyl inositol 3-kinase; TMZ, temozolomide; Temozolomide; Vimentin