title: RNAi for contactin 2 inhibits proliferation of U87-glioma stem cells by downregulating AICD, EGFR, and HES1.
abstract: Glioblastoma is the most common form of malignant brain tumors and has a poor prognosis. Glioma stem cells (GSCs) are thought to be responsible for the aberrant proliferation and invasion. Targeting the signaling pathways that promote proliferation in GSCs is one of the strategies for glioma treatment. In this study, we found increased expression of contactin 2 (CNTN2) and amyloid β precursor protein (APP) in U87-derived GSCs (U87-GSCs). RNA interference (RNAi) forCNTN2downregulated the expression of APP intracellular domain (AICD), which is the proteolytic product of APP. Treatment withCNTN2RNAi inhibited the proliferation of U87-GSCs.CNTN2RNAi decreased the expression of epidermal growth factor receptor and HES1, which are potential targets of AICD. In summary, inhibition of the CNTN2/APP signaling pathway may repress the proliferation in U87-GSCs via downregulating the expression of HES1 and epidermal growth factor receptor. CNTN2/APP/AICD signaling pathway plays an important role in U87 glial tumorigenesis. Further studies are warranted to elucidate the role of these signaling pathways in other sources of GSCs. Depending on their role in proliferation in other sources of GSCs, members of the CNTN2/APP/AICD signaling pathway may provide novel targets for the development of therapy for glioblastomas.
authors.affiliation: Department of Neurology.
authors.forename: Yang
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of Cardiovascular Medicine, Zhujiang Hospital; Second Clinical Medical College, Southern Medical University, Guangzhou.
authors.forename: Peidong
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Affiliated Bayi Brain Hospital, The Military General Hospital of Beijing PLA, The Bayi Clinical Medical Institute of Southern Medical University, Beijing, People's Republic of China.
authors.forename: Hongtian
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Affiliated Bayi Brain Hospital, The Military General Hospital of Beijing PLA, The Bayi Clinical Medical Institute of Southern Medical University, Beijing, People's Republic of China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Affiliated Bayi Brain Hospital, The Military General Hospital of Beijing PLA, The Bayi Clinical Medical Institute of Southern Medical University, Beijing, People's Republic of China.
authors.forename: Ruxiang
authors.initials: R
authors.lastname: Xu
keywords: CNTN2; TAG1; contactin 2; glioma stem cells; transient axonal glycoprotein-1