Pre-B-cell leukemia homeobox interacting protein 1 is overexpressed in astrocytoma and promotes tumor cell growth and migration.
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.


CONCLUSIONS
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.
Dannis G
DG
van Vuurden
Eleonora
E
Aronica
Esther
E
Hulleman
Laurine E
LE
Wedekind
Dennis
D
Biesmans
Arjan
A
Malekzadeh
Marianna
M
Bugiani
Dirk
D
Geerts
David P
DP
Noske
W Peter
WP
Vandertop
Gertjan J L
GJ
Kaspers
Jacqueline
J
Cloos
Thomas
T
Würdinger
Petra P M
PP
van der Stoop
D000328:Adult; D001254:Astrocytoma / Q000378:metabolism / Q000473:pathology*; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology*; D049109:Cell Proliferation; D002648:Child; D056970:Co-Repressor Proteins; D005260:Female; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008856:Microscopy, Fluorescence; D009361:Neoplasm Invasiveness / Q000473:pathology*; D020411:Oligonucleotide Array Sequence Analysis; D040901:Proteomics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D046888:Tissue Array Analysis; D014157:Transcription Factors / Q000096:biosynthesis*; D015854:Up-Regulation
D056970:Co-Repressor Proteins; C413449:PBXIP1 protein, human; D014157:Transcription Factors