TY - JOUR
T1 - Pre-B-cell leukemia homeobox interacting protein 1 is overexpressed in astrocytoma and promotes tumor cell growth and migration
AU - van Vuurden, Dannis G
AU - Aronica, Eleonora
AU - Hulleman, Esther
AU - Wedekind, Laurine E
AU - Biesmans, Dennis
AU - Malekzadeh, Arjan
AU - Bugiani, Marianna
AU - Geerts, Dirk
AU - Noske, David P
AU - Vandertop, W Peter
AU - Kaspers, Gertjan J L
AU - Cloos, Jacqueline
AU - Würdinger, Thomas
AU - van der Stoop, Petra P M
PY - 2014/7
Y1 - 2014/7
N2 - BACKGROUND: Glial brain tumors cause considerable mortality and morbidity in children and adults. Innovative targets for therapy are needed to improve survival and reduce long-term sequelae. The aim of this study was to find a candidate tumor-promoting protein, abundantly expressed in tumor cells but not in normal brain tissues, as a potential target for therapy.METHODS: In silico proteomics and genomics, immunohistochemistry, and immunofluorescence microscopy validation were performed. RNA interference was used to ascertain the functional role of the overexpressed candidate target protein.RESULTS: In silico proteomics and genomics revealed pre-B-cell leukemia homeobox (PBX) interacting protein 1 (PBXIP1) overexpression in adult and childhood high-grade glioma and ependymoma compared with normal brain. PBXIP1 is a PBX-family interacting microtubule-binding protein with a putative role in migration and proliferation of cancer cells. Immunohistochemical studies in glial tumors validated PBXIP1 expression in astrocytoma and ependymoma but not in oligodendroglioma. RNAi-mediated PBXIP1-knockdown in glioblastoma cell lines strongly reduced proliferation and migration and induced morphological changes, indicating that PBXIP1 knockdown decreases glioma cell viability and motility through rearrangements of the actin cytoskeleton. Furthermore, expression of PBXIP1 was observed in radial glia and astrocytic progenitor cells in human fetal tissues, suggesting that PBXIP1 is an astroglial progenitor cell marker during human embryonic development.CONCLUSION: PBXIP1 is a novel protein overexpressed in astrocytoma and ependymoma, involved in tumor cell proliferation and migration, that warrants further exploration as a novel therapeutic target in these tumors.
AB - BACKGROUND: Glial brain tumors cause considerable mortality and morbidity in children and adults. Innovative targets for therapy are needed to improve survival and reduce long-term sequelae. The aim of this study was to find a candidate tumor-promoting protein, abundantly expressed in tumor cells but not in normal brain tissues, as a potential target for therapy.METHODS: In silico proteomics and genomics, immunohistochemistry, and immunofluorescence microscopy validation were performed. RNA interference was used to ascertain the functional role of the overexpressed candidate target protein.RESULTS: In silico proteomics and genomics revealed pre-B-cell leukemia homeobox (PBX) interacting protein 1 (PBXIP1) overexpression in adult and childhood high-grade glioma and ependymoma compared with normal brain. PBXIP1 is a PBX-family interacting microtubule-binding protein with a putative role in migration and proliferation of cancer cells. Immunohistochemical studies in glial tumors validated PBXIP1 expression in astrocytoma and ependymoma but not in oligodendroglioma. RNAi-mediated PBXIP1-knockdown in glioblastoma cell lines strongly reduced proliferation and migration and induced morphological changes, indicating that PBXIP1 knockdown decreases glioma cell viability and motility through rearrangements of the actin cytoskeleton. Furthermore, expression of PBXIP1 was observed in radial glia and astrocytic progenitor cells in human fetal tissues, suggesting that PBXIP1 is an astroglial progenitor cell marker during human embryonic development.CONCLUSION: PBXIP1 is a novel protein overexpressed in astrocytoma and ependymoma, involved in tumor cell proliferation and migration, that warrants further exploration as a novel therapeutic target in these tumors.
KW - Adult
KW - Astrocytoma/metabolism
KW - Blotting, Western
KW - Brain Neoplasms/metabolism
KW - Cell Proliferation
KW - Child
KW - Co-Repressor Proteins
KW - Female
KW - Flow Cytometry
KW - Gene Expression Profiling
KW - Humans
KW - Immunohistochemistry
KW - Male
KW - Microscopy, Fluorescence
KW - Neoplasm Invasiveness/pathology
KW - Oligonucleotide Array Sequence Analysis
KW - Proteomics
KW - Real-Time Polymerase Chain Reaction
KW - Reverse Transcriptase Polymerase Chain Reaction
KW - Tissue Array Analysis
KW - Transcription Factors/biosynthesis
KW - Up-Regulation
U2 - 10.1093/neuonc/not308
DO - 10.1093/neuonc/not308
M3 - Article
C2 - 24470547
SN - 1522-8517
VL - 16
SP - 946
EP - 959
JO - Neuro-Oncology
JF - Neuro-Oncology
IS - 7
ER -